"FiSHing for a Cure" News and Updates

Need muscle for a tough spot?

2012-01-30T17:28:00.000-08:00

Need muscle for a tough spot? Turn to fat stem cells

ScienceDaily (Jan. 30, 2012) — Stem cells derived from fat have a surprising trick up their sleeves: Encouraged to develop on a stiff surface, they undergo a remarkable transformation toward becoming mature muscle cells. The new research appears in the journal Biomaterials. The new cells remain intact and fused together even when transferred to an extremely stiff, bone-like surface, which has University of California, San Diego bioengineering professor Adam Engler and colleagues intrigued. These cells, they suggest, could hint at new therapeutic possibilities for muscular dystrophy.

Thanks for the Great Event - January 28th

2012-01-30T17:20:00.000-08:00

Friends of FSH Research

THANK YOU!!

You, the many friends of FSH research, raised $161,500 on January 28th!

Thank You!

Your Generous Support Made the Difference!!

THANK YOU!!

The UW All Star Jazz Quartet featuring

Michael Brockman

and

THANK YOU!

THE OFFENDERS

for spinning the tunes of the '60s & '70s

THANK YOU

Our Auctioneer David Silverman and Emcee Wendy Boglioli

for making our event fun, engaging and wildly successful!

THANK YOU

to our fabulous volunteers

We could not have done this without you!

Teams closing in on gene behind FSHD - FierceBiomarkers

2012-01-22T17:16:00.000-08:00

Teams closing in on gene behind form of muscular dystrophy - FierceBiomarkers

Teams closing in on gene behind form of muscular dystrophy

January 18, 2012 — 6:44am ET | By Suzanne Elvidge

TOOLS

While exactly which gene actually causes facioscapulohumeral muscular dystrophy (FSHD), the third most common inherited form of dystrophy, isn't clear, researchers at the Fred Hutchinson Cancer Research Center are looking at the gene for the DUX4 transcription factor as a potential candidate.

The symptoms of FSHD affect the upper body and can start with eyelid drooping and inability to whistle. People then develop arm and upper body weakness, and this can even affect walking if the symptoms are severe. Fortunately, for most people, the disability is minor.

When the researchers looked at muscle cells, the DUX4 genes were active in the cells from people with FSHD but not in the cells from healthy people, which suggests that changes in this gene could contribute to causing the disease—the evidence of the genetic link was described by one of the researchers as "about as strong of evidence as you can get."

"This study is a significant step forward by solidifying that the DUX4 transcription factor causes this disease, while offering a number of viable mechanisms for why the muscle is damaged," said corresponding author Dr. Stephen Tapscott, Ph.D., a member of the Hutchinson Center's Human Biology Division.

The identification of this biomarker could lead to possible diagnostics for FSHD, both to identify the disease and to check its progression, as well as support for the development of drugs to treat the disorder. Because DUX4 is also linked with cancer, its identification could also help the development of cancer immunotherapies and vaccines.

- read the press release

Read more: Teams closing in on gene behind form of muscular dystrophy - FierceBiomarkers http://www.fiercebiomarkers.com/story/teams-closing-gene-behind-form-muscular-dystrophy/2012-01-18#ixzz1kEvj9wbQ
Subscribe: http://www.fiercebiomarkers.com/signup?sourceform=Viral-Tynt-FierceBiomarkers-FierceBiomarkers

DUX4 Causes Muscle Mayhem in FSHD

2012-01-21T08:49:00.000-08:00

DUX4 Causes Muscle Mayhem in FSHD | Quest Magazine Online

Article Highlights:

A multicenter research team has provided specific evidence that inappropriate production of DUX4 in muscle is a major contributor to FSH dystrophy.
DUX4 disrupts numerous biochemical pathways in muscle, interfering with the ability of muscle cells to develop and thrive.
Interfering with DUX4 is a promising strategy for the treatment of FSHD.
Measuring DUX4-related biochemical changes in the body could provide researchers with new biomarkers with which to follow disease progression and response to treatment.

Kirkland Family Raises Funds for FSH Research

2012-01-18T19:47:00.000-08:00

Kirkland Weblog

Kirkland Family Raises Funds for FSH Research

Terry Colella has lived in the same Kirkland home since 1980. But in 2004, everything changed when her son, Brian, was diagnosed with FSH (Facioscapulohumeral Muscular Dystrophy) and they turned from your typical Kirkland family looking forward to college and grandchildren, into one of fundraisers. What they discovered was that very few researchers were studying this condition due to lack of funds and its complexity. This family does not sit and ponder. Now they head up a non-profit charity,Friends of FSH Research, and raise money for research.

They have raised more than $1.5M from their home-based charity with a volunteer crew. Today, researchers at the Fred Hutchinson Research Center and the University of WA are leaders in FSH research and are working in collaboration with researchers in the Netherlands and Rochester, NY as a result of their funding and support.

Please consider joining the Colellas for the 8th annual gala auction event to benefit FSH on January 28th at 5pm/Bellevue Hyatt. There will be a silent auction, champagne/appetizers, 4 course gourmet dinner with wine and a live auction led by auctioneer David Silverman. 1976 Gold Medalist Wendy Boglioli will be emcee for the evening. And local band The Offenders will be playing after the auction so don't forget your dancing shoes! Tickets are $110/per person and parking is free. 100% of the proceeds from the event go towards supporting FSH research. Purchase online or call 425-827-8954.

January 18, 2012 in Kirkland Events , Kirkland General Topics, Kirkland Health and Fitness | Permalink | Comments (0) | TrackBack (0)

Joel Chamberlain RNAi Update

2012-01-17T18:06:00.000-08:00

Joel Chamberlain RNAi Update - Read about this research http://www.fshfriends.org/Education/News/news00043.html

2010 Collaborative Grant - An Effective Means of Utilizing Limited Funds

2012-01-17T09:11:00.000-08:00

Collaborative Grant to University of Washington

Researcher to Speed Therapy Development for FSH Dystrophy

Although this is the news about a jointly-funded project in 2010-2012, it is out hope that more collaboration between funding groups will happen in the coming years. It is an effective way to stimulate new projects, increase awareness of a condition and maximize our funds. Here is one example of how groups can work together effectively.

T.C.

Collaborative Grant to University of Washington Researcher to
Speed Therapy Development for FSH Dystrophy

TUCSON, Ariz., and KIRKLAND, Wash., April 5, 2010 ─ The Muscular Dystrophy Association (MDA), headquartered in Tucson, Ariz., and Friends of FSH Research (FFSHR), based in Kirkland, Wash., today jointly awarded a two-year, $200,000 grant to Joel Chamberlain, research assistant professor of medical genetics at the University of Washington. The grant, equally funded by the two organizations, will enable the laboratory led by Dr. Chamberlain to study RNA interference as an investigative and therapeutic tool forfacioscapulohumeral muscular dystrophy.

“We’re delighted to be funding this cutting-edge research aimed at finding a therapy for FSH dystrophy,” says Valerie Cwik, MDA Executive Vice President – Research and Medical Director. “Not only might this project identify the precise molecular cause of FSHD — which has eluded us — but it could also rapidly suggest a viable therapeutic approach to the disease.”

Last fall, MDA and FFSHR teamed up to issue a worldwide request for applications (RFA) for projects targeting the identification, prioritization and/or validation of molecular targets for potential therapies for FSH dystrophy. The goal is to stimulate a new wave of innovative FSH dystrophy research to help people affected by the progressive neuromuscular disease, which can cause weakness in the upper body, lower leg, hip or abdominal muscles; hearing loss; and retinal eyesight, heart or respiratory muscle abnormalities.

“Our RFA is proving to be a strong catalyst for vital research,” notes Terry Colella, FFSHR President. “We’re creating new momentum in the field of FSH dystrophy research and Dr. Chamberlain’s work should quickly bring us closer to a much needed therapy or cure.”

The Chamberlain project will focus on the recently discovered biological process, called RNA interference (RNAi), that cells normally use to fine-tune the levels of proteins that carry out body functions. “We’re developing ways to harness the potential for directed RNAi to turn off production of specific proteins in muscle that are thought to cause FSH dystrophy,” explains Chamberlain. “Thanks to funding from MDA and Friends of FSH Research, we soon should be ready to target promising therapies to attack this disease.”

A second notable FSH research project also was identified as a result of the joint RFA distributed by MDA and FFSH Research. That meritorious project, led by Silvere van der Maarel at Leiden University Medical Center in the Netherlands, is being funded by MDA and will use a slightly different approach (antisense oligonucleotides) to develop potential treatments for FSH dystrophy.

Leveraging Prior Insights

The exciting new initiatives will benefit from decades of FSH dystrophy research seeking the elusive genetic cause of FSH dystrophy and defining the varied course of the disease. Notable advances made by investigators benefiting from MDA’s more than $16 million investment in FSH dystrophy research since 1987 include:

mapping the genetic mutation causing FSH dystrophy to a small region near one end of chromosome 4;
determining that many genes are incorrectly regulated in muscles affected by FSH dystrophy;
finding that abnormal DNA in the disease-associated region of chromosome 4 inappropriately activates gene expression in FSH dystrophy; and
discovering that an unusual looping of chromosome 4, marked by an abnormally short D4Z4 region, has widespread consequences for gene regulation in FSH dystrophy.

About Friends of FSH Research

Friends of FSH Research was formed by the family and friends of Brian Colella, who was diagnosed with facioscapulohumeral dystrophy, or FSHD, in 2004. As an independent, 501(c)(3) nonprofit tax-exempt organization, the organization’s goal is to raise money to help fund researchers trying to decode the genetic mysteries of FSHD so that a treatment or cure can be developed.

Friends of FSH Research was created because there is a need for additional funds for FSHD research. To stimulate new research and support for current researchers in this field, it was essential that a fundraising organization be founded. Friends of FSH Research is excited by the opportunity to help those affected by this disabling condition by funding scientists researching FSHD, and we feel very lucky to have established a partnership with the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center at the University of Washington.

About MDA

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association, which maintains a network of more than 200 hospital-affiliated clinics nationwide, also provides comprehensive health care and support services, advocacy and education.

Founded in 1950, MDA is the nation’s largest nongovernmental funder of research seeking treatments and cures for more than 40 neuromuscular diseases, including muscular dystrophy, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Charcot-Marie-Tooth disease (CMT), and Friedreich’s ataxia (FA).

The first nonprofit organization to be recognized with a Lifetime Achievement Award from the American Medical Association (“for significant and lasting contributions to the health and welfare of humanity”), MDA’s annual investment in research exceeds $40 million.

Thanks to decades of generous contributions from caring individuals, plus outstanding support received from local, regional and national sponsors, MDA is credited for its role in building the entire field of neuromuscular disease research, while simultaneously nurturing clinical care to significantly improve both quality and length of life for those affected by neuromuscular diseases.

Facioscapulohumeral muscular dystrophy: New diagnostic strategies

2012-01-16T09:35:00.000-08:00

Facioscapulohumeral muscular dystrophy: New diagnostic strategies for complicated cases

The diagnosis of FSHD is usually straightforward because the muscle groups are affected in a very specific pattern. However, some patients may have symptoms that superficially resemble FSHD, but is actually a different condition. Even the most experienced clinician can sometimes be fooled by such 'look-alike' cases.

Read the entire article to learn more.

Friends of FSH Research Funded Project

2012-01-15T11:30:00.000-08:00

Friends of FSH Research Funded Projects in Tapscott Lab at FHCRC

Major advances in research over the last two years have determined that FSHD is caused by the aberrant expression of the DUX4 gene in skeletal muscle. DUX4 is normally expressed in germline cells and early development, but tissues in the adult completely suppress the expression of DUX4. In FSHD the suppression is incomplete and DUX4 is expressed in mature skeletal muscle. Recent work in the Tapscott lab has shown that DUX4 normally regulates the expression of germline and stem cell genes and that the mis-expression of DUX4 in skeletal muscle activates that expression of these early developmental genes. Work recently funded by Friends of FSH Research will use these findings to develop the components necessary to identify drugs that prevent the DUX4 expression and/or DUX4-induced damage in muscle cells. The Tapscott lab plans to develop several ways to measure DUX4 expression and toxicity, and then perform tests to see how well each can be used for a large-scale screen of possible drugs. As the tests are validated it is anticipated that pharmaceutical companies might adopt them to screen their extensive libraries of drug-like compounds.

— Stephen Tapscott

Research team discovers genes and disease mechanisms behind a FSH muscular dystrophy

2012-01-12T09:59:00.000-08:00

Research team discovers genes and disease mechanisms behind FSHD Muscular Dystrophy - Seattle Researchers!

Support to Friends of FSH Research IS making a difference!!! Please consider making a donation today!!

SEATTLE – Continuing a series of groundbreaking discoveries begun in 2010 about the genetic causes of the third most common form of inherited muscular dystrophy, an international team of researchers led by a scientist at Fred Hutchinson Cancer Research Center has identified the genes and proteins that damage muscle cells, as well as the mechanisms that can cause the disease. The findings are online and will be reported in the Jan. 17 print edition of the journal Developmental Cell.

The discovery could lead to a biomarker-based test for diagnosing facioscapulohumeral muscular dystrophy (FSHD), and the findings have implications for developing future treatments as well as for cancer immunotherapies in general.

The work establishes a viable roadmap for how the expression of the DUX4 gene can cause FSHD. Whether this is the sole cause of FSHD is not known; however, the latest findings "are about as strong of evidence as you can get" of the genetic link, said corresponding author Stephen Tapscott, M.D., Ph.D., a member of the Hutchinson Center's Human Biology Division.

Tapscott and colleagues sought answers to the questions about what the DUX4 protein does both normally in the body and in the FSHD disease process. In the latest study, they identified that the DUX4 protein regulates many genes that are normally expressed in the male germ line but are abnormally expressed in FSHD muscle. Germ line cells are inherited from parents and passed down to their offspring.

"This study is a significant step forward by solidifying that the DUX4 transcription factor causes this disease, while offering a number of viable mechanisms for why the muscle is damaged," Tapscott said. Transcription factors are tools that cells use to control gene expression. Genes that are "turned on" in the body are "transcribed," or translated, into proteins.

Now that scientists know that targets for DUX4 are expressed in skeletal muscle, an antibody- or RNA-based test could be developed to diagnose FSHD by examining muscle tissue from a biopsy, Tapscott said. Such biomarker-based tests also could be used to determine how well new treatments are working to suppress FSHD.

The study also discovered that DUX4 regulates cancer/testis antigens. Cancer/testis antigens are encoded by genes that are normally expressed only in the human germ line, but are also abnormally expressed in various tumor types, including melanoma and carcinomas of the bladder, lung and liver.

"This knowledge now gives us a way to manipulate the expression of cancer/ testis antigens, potentially opening the opportunity to use these antigens in a cancer vaccine," Tapscott said.

Two papers published in 2010 by the same group of researchers established the genetic basis for showing that expression of DUX4 was necessary for the disease. The previous research also identified the RNA in the FSHD muscles and showed that it was normally expressed in the germ line, which led to the hypothesis that the lack of an efficient developmental repression of this RNA caused the disease.

###

In addition to Tapscott and other Hutchinson Center researchers, scientists from Leiden University Medical Center in Leiden, The Netherlands; University of Washington; Genentech; and the University of Rochester contributed to the study.

The research was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Neurological Disorders and Stroke, and Friends of FSH Research.

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.

Discovery Could Lead to an Exercise Pill - Technology Review

2012-01-11T17:38:00.000-08:00

Discovery Could Lead to an Exercise Pill - Technology Review

Researchers have discovered a natural hormone that acts like exercise on muscle tissue—burning calories, improving insulin processing, and perhaps boosting strength. The scientists hope it could eventually be used as a treatment for obesity, diabetes, and, potentially, neuromuscular diseases like muscular dystrophy.

More news coming that may be of help to those with neuromuscular disorders.

DUX4 Activates Germline Genes - Research Supported by Friends of FSH Research

2012-01-01T15:02:00.000-08:00

Developmental Cell - DUX4 Activates Germline Genes, Retroelements, and Immune Mediators: Implications for Facioscapulohumeral Dystrophy

Previous work by Tapscott's lab (Snider, et al., 2010) showed that the DUX4 gene is normally expressed in germline cells of the human testes and is not normally expressed in other tissues in the adult, whereas in both FSHD1 and FSHD2 small amounts of DUX4 are expressed in muscle cells. In a new study recently published in the journal Developmental Cell, the research group identified genes that are regulated by DUX4 and detected the expression of these genes in FSHD muscle, "providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD." This publication demonstrates that the low levels of DUX4 expressed in FSHD muscle has a domino effect, activating many genes. This allows for the identification of several biomarkers to track the progress of FSHD, and to determine the efficacy of treatment. In addition, the genes regulated by DUX4 suggest several mechanisms for the loss of muscle strength in FSHD and these can be tested as candidate targets for new therapies. This is a major turning point, both identifying how DUX4 damages muscle in FSHD as the basis for developing therapies, and also a providing a set of biomarkers to easily determine if candidate therapies are actually working.

Refer to the Developmental Cell article.

Advances in FSHD Research

2011-11-29T09:36:00.000-08:00

New advances in FSHD research | The Leaders in FSHD research Today!

On November 7 and 8, eighty scientists met in Boston, Massachusetts, to share the latest results from their research on facioscapulohumeral muscular dystrophy (FSHD). This conference is hosted annually by the American . Andreas Leidenroth, a Muscular Dystrophy Campaign-funded PhD student researching FSHD in Nottingham, attended the conference and here he reports on two important highlights presented at the meeting.

The highlights mentioned by this researcher are those achieved by researchers Friends of FSH Research has worked closely with since 2006!

Read this report - Dr. Tapscott and the Seattle FSH Research group has worked in collaboration with the researchers in Leiden for many years.

Friends of FSH Research has held an annual FSH workshop bringing these groups together & urging strong collaborative efforts in order to speed up the progress of FSH research.

Make a donation to Friends of FSH Research Today!

It DOES make a difference.

Meeting with Bill Moss

2011-11-25T12:51:00.000-08:00

Video Discussion with Bill Moss

Here is a personal look at Bill Moss - in his own words.
Mr. Moss has become a leader for those with FSH Muscular Dystrophy - putting his influence to help move this research forward worldwide.

Grants & Gala - Support FSH Research

2011-11-17T13:32:00.000-08:00

Thank You!! (click here to see November news)

Your past support has been critical to the stimulation of new interest in Facioscapulohumeral (FSH) research. You have helped to attract research scientists and to fund novel FSH projects that have expanded the world's understanding of the mechanisms at work in this form of Muscular Dystrophy.

Our 8th annual charity gala is dedicated to YOU, our community.

The dinner and auction will be held at the Bellevue Hyatt on January 28th. The theme of this year's gala, "With a Little Help from Our Friends," honors our community and its generous support.
We invite you to join with us as we celebrate our successes and your partnership.

Progress has been made! We will need your continued support to achieve our next goal, the development of an effective therapy for FSH Muscular Dystrophy.

FSHD Europe: The European voice of people with FSHD

2011-11-08T11:01:00.000-08:00

FSHD Europe: The European voice of people with FSHD

The European FSHD advocacy groups have joined together - here is their newly developed website.

We are pleased that the video Friends of FSH Research produced is presented on their learning about FSHD page.

Working together we will find a treatment or cure for FSHD.

PLOS Research Report - FSHD

2011-11-05T11:42:00.000-07:00

Scientific Publications Explained

Title: The FSHD Atrophic Myotube Phenotype Is Caused by DUX4 Expression

Authors: Vanderplanck C, Ansseau E, Charron S, Stricwant N, Tassin A, Laoudj-Chenivesse D, Wilton SD, Coppée F, Belayew A.

Publication date and journal: 28 Oct 2011 in PLos One

This work was done by the group of Alexandra Belayew in Mons, Belgium, in collaboration with Dalila Laoudj-Chenivesse from Montpellier, France, and Professor Steve D. Wilton from Perth, Australia, who does much work with exon skipping in Duchenne. Muscle cells of healthy individuals cultured in the laboratory in which DUX4 was introduced were much thinner (atrophic) than muscle cells without active DUX4. (Such thin muscle cells are seen in FSHD.) A number of genes characteristic for the diseased muscle were also found to be activated (Atrogin1, MuRF1, CRYM and TP53). These genes may be used to measure the effect of drugs.

Next, the researcher developed siRNA molecules against DUX4 (these are molecules that cause degradation of the DUX4 messenger RNA so no more DUX4 protein is made). Muscle cells cultured in the laboratory with active DUX4 which were treated with this anti-DUX4 siRNA were less thin 8 days after treatment than untreated muscle cells. They made less DUX4 and TP53 proteins. Antisense Oligonucleotides (AOs) were then developed against DUX4. This is a different kind of anti-molecule which is used for exon skipping in Duchenne. Muscle cells from people with FSHD cultured in the laboratory and treated with a low concentration of anti-DUX4 AOs had less DUX4 and TP53, without much effect on DUX4c, a gene similar to DUX4 which probably has an important function in the human body.

The group of Alexandra Belayew and other research groups worldwide are now working on developing DUX4 mouse models to test whether these anti-DUX4 molecules can slow, stop or hopefully even improve the health of diseased animals.

Click on "PLOS ONE" to read complete study report

Thank You for Being a Friend

2011-11-04T20:27:00.000-07:00

After tough voting in a facebook contest, our charity Friends of FSH Research won $5,000 from the Toyota of Kirkland dealership. Thanks to all the voters that took the time to “like” our charity, we were the top vote getters and the winners of this grant from Toyota.

Our charity auction’s theme this year is “With a Little Help from Our Friends.” Though it might be a song with some questionable references, for us it is a song that celebrates friends. It has taken the support of many friends to push our mission forward toward finding a treatment or cure for FSH Muscular Dystrophy. And now, our circle of friends just got bigger – thank you Toyota of Kirkland for being a friend!

Good Search for FSH Research

2011-10-19T10:17:00.001-07:00

This is going to be the easiest thing we’ve ever asked you to do!

We just signed up with GoodSearch.com and now every time you shop online or search the internet, a donation will be made to Friends of FSH Research.

Here’s how:

GoodShop.com works with more than 2,500 stores (including Target, Apple, Petsmart etc..) and every time you purchase something, a percentage will be donated to us! And, even more exciting, GoodShop also offers over 100,000 of the most up-to-date coupons and free shipping offers so you can save money at the same time. It’s win win.

GoodSearch is a Yahoo powered search engine which makes a donation to us each time you do a search.

“Become a Supporter” button

Join the rest of our community in using these sites to help us easily raise money for our mission. Get started by clicking the Good Search information

on our website!

Whooping Cough - Risk to the Vulnerable

2011-10-10T11:30:00.000-07:00

Whooping Cough (or Pertusis) is on the rise. As vaccines seem to lose effectiveness over time, adults need Pertusis booster every 10 years. Whooping Cough, also known as the 100 day cough, may not have serious consequences for healthy people but this condition can be life threatening for infants or vulnerable individuals. Get immunized!!

14 percent increase in WA whooping cough cases

www.king5.com

The Washington state Health Department says 431 cases have been reported so far this year, compared with 378 at this time last year.

Collaborating Research Teams - Progress toward FSH Treatment

2011-08-27T12:05:00.000-07:00

Two research teams make steps towards a treatment for FSH

Two research papers published in the past month by researchers in Italy and the US have shown that it is possible to reverse the symptoms of facioscapulohumeral muscular dystrophy (FSH) in a mouse model using a gene therapy approach. The techniques used may also be applicable to other dominantly inherited muscle conditions such as myotonic dystrophy, oculopharyngeal muscular dystrophy (OPMD), Charcot-Marie-Tooth disease and some types of limb girdle muscular dystrophy, congenital muscular dystrophy and congenital myopathy.

Background information

FSH is caused by changes to a region of DNA on chromosome 4 called D4Z4 that has the same piece of DNA code repeated many times. In healthy individuals the number of repeats varies between 11 and 100. People with FSH have less than 11 repeats. Until recently scientists have struggled to understand how this caused the symptoms of the condition.

Recent research demonstrated that the repeated section of DNA contains a gene called DUX4 and the reduction in the number of repeats on D4Z4 changes the way this piece of DNA is folded. This results in the DUX4 gene being switched on and the DUX4 protein being produced which is toxic to the muscle.

Although this is currently the most widely accepted theory about the underlying mechanism causing FSH, previous research has also shown that neighbouring genes such as one called FRG1 may also be involved. It has been proposed by some researchers that FRG1 is switched on in FSH which is toxic to the muscles. The importance of FRG1 in causing the symptoms of FSH in humans is still controversial though, because it hasn't been proven beyond doubt that it is involved.

What did the research show?

This research took advantage of natural processes in the body which regulate which genes are switched on and which are off. When a gene is 'switched on', RNA 'photocopies' of the gene's code are made. The RNA moves outside the nucleus where they direct the manufacture of proteins. DNA can be thought of as a recipe book in the library that you can't take out. RNA is a photocopy of a recipe that you can take home to cook something in your kitchen (making the protein).

The new potential therapies involve switching off a gene so that the RNA copy is not made. This is called "RNA interference" or "gene silencing". It involves introducing into the cell tiny pieces of genetic material called "micro RNA" or "short hairpin RNA" that are designed to specifically switch off a particular gene. Although the strategy was similar in the two studies, the design of the microRNA was different.

Both research groups tested their new potential therapy in the only available mouse model for FSH - the FRG1 mouse. These mice have increased levels of FRG1 and develop muscle wasting and weakness.

Adeno-associated viruses (AAV) were used to deliver micro RNA that was designed to switch off the FRG1 gene into the cells of the mice. AAV is currently the most attractive candidate for gene therapy because it is not known to cause any severe disease in humans and is capable of infecting many different cell types including muscle cells.

Both studies reported that after the RNA interference treatment, the mouse muscles not only looked healthier under a microscope but their muscle size and strength was improved. For example in one study they measured how long the mice could run on a treadmill before they got tired. Untreated 12-week-old mice could only run for about 15 minutes whereas those that had been treated with the RNA interference were able to run for almost 25 minutes; on a par with healthy mice. One of the studies also included extensive toxicity monitoring and they concluded that the treatment appeared to be safe in mice.

What does this mean for FSH patients?

This research is exciting because it proves the principle that RNA interference is a promising therapeutic approach for FSH. One of the challenges of treating any muscle condition is to deliver the drug to all of the muscles of the body which make up a large proportion of our body mass. These studies were able to show that it is possible deliver the RNA efficiently to the muscles using a virus and this had a positive effect on muscle function.

Whether FRG1 is the correct target for a FSH therapy is still uncertain and more research is required to understand its role. However, the authors of these studies said that this technology could easily be applied to other target genes such as DUX4. Researchers are currently working to develop a DUX4 mouse model that would allow this to be tested.

RNA interference is very new technology and although there have been promising results from animal models, in particular for neurodegenerative conditions, no drugs have reached the clinic yet. Therefore, it may be several years before it is ready for testing in patients.

This strategy is similar to the exon skipping that is in clinical trial for Duchenne muscular dystrophy. Both strategies involve delivering small pieces of genetic material to change the way genes function. The difference is that for Duchenne muscular dystrophy a gene is repaired, whereas with for FSH a gene is switched off. The recent positive results in the Duchenne clinical trials will spur on researchers working on this strategy and inform them on ways to move this therapy forward to the clinic.

What about other conditions?

It is only in recent years that scientists have started to understand more about how genes are switched off which has opened up the prospect of treating conditions that result in the production of harmful RNA or protein.

RNA interference could potentially be used to treat many other muscle conditions where the faulty gene has toxic effects on the muscle or interferes with the functioning of other healthy genes. These conditions are inherited in an "autosomal dominant" way, which means that only one faulty gene, inherited from either parent, is required to cause the condition.

Examples include myotonic dystrophy, oculopharyngeal muscular dystrophy (OPMD), Charcot-Marie-Tooth disease and some types of limb girdle muscular dystrophy, congenital muscular dystrophy and congenital myopathy. However, each affected gene will need to be looked at on a case by case basis, and researched in the laboratory before it can decided if it could possibly be amenable to RNA interference.

Considerable research has already been done in a mouse model of myotonic dystrophy using small pieces of DNA. Although closely related, that research was not the same as RNA interference. It involved blocking the interaction between RNA and proteins, rather than switching off the production of the RNA in the first place, which would be the case with RNA interference. So RNA interference adds another line of attack to the potential therapies currently being researched for myotonic dystrophy.

Article cited from: http://www.muscular-dystrophy.org/

Funding for Davide Gabelini's work provided by Muscular Dystrophy Campaign, UK

Big Stories - No Takers

2011-08-15T13:37:00.000-07:00

It is perplexing how to get today's news organizations to pick up and share stories with their readers.....As a small, non-profit we have helped to fund research that is making major breakthroughs yet, the Seattle public has no idea that this work is being done in their own backyard. Last year researchers here (at the Hutch & UW) in collaboration with scientists in the Netherlands & Rochester, NY made a huge breakthrough in Facioscapulohumeral (FSH) Muscular Dystrophy research - it made news in New York, being a featured story in the New York Times yet, Seattle readers were left in the dark.

It is amazing the progress we have made - functioning from our home on a "all volunteer" basis without getting the support from our local press. Yet, our organization Friends of FSH Research (www.fshfriends.org) has been able to raise over a million dollars for FSH research and has helped launch pilot projects which generated new data, their findings which earned the respect and funding from the National Institutes of Health.

Facioscapulohumeral (FSH) Muscular Dystrophy, today believed to be the most common form of Muscular Dystrophy, (who knew that there are more than one form?) has received little research support in the past from the existing funding sources. This condition impacts the lives of those affected throughout their life span - causing a weakening then ultimately the death of the muscles of the upper back, upper arms and face. Eventually the muscle destruction extends into the muscles of the lower legs and trunk .... it is an unforgiving condition. Not a sexy condition, not one which attracts media attention... one often overlooked, forgotten.

Friends of FSH Research proves the "Power of One" - one family, one love for their child. We would not have been able to succeed without the internet, social media and the community. This is one story that has not yet been helped by traditional media - though I am still hopeful that one day they will pick up our story for I think it is one worthy of telling.

FSHD and Standing Frame Exercise

2011-08-05T11:34:00.000-07:00

FSHD and Standing Frame Exercise : Progressive Muscular Dystrophy

Standing Frame Exercises
People with FSHD may also benefit from exercises carried out using the support of the system known as a standing frame, which is designed to support a person with mobility restrictions stand and then remain in a standing position. potential advantages of using a standing frame include preserving some range of motion, enhancing bone strength, growing blood circulation and realigning the position within the inner organs. Other possible advantages include worry reduction and lowered risks for any form of abnormal muscle and tendon shortening known as contracture.

Generosity of Strangers and Old Friends - Amazing Grace

2011-08-01T10:01:00.000-07:00

THANK YOU!! Spent the weekend sharing our story with artists at the Bellevue Art Festival. I am touched that so many individuals were willing to donate their artwork to us for our January auction. The generosity and kindness we have received has been amazing ... although the work of procurement is certainly not an easy one, I am forever grateful.
I will start posting pictures and website links of the artists over the coming weeks - Please check out their artwork!

Chris Carrino Foundation - The Power of One

2011-07-20T15:45:00.000-07:00

Chris Carrino: Alumnus and Broadcaster's Personal Battle Becomes Public

Carrino has been battling Facioscapulohumeral Muscular Dystrophy (FSHD), a debilitating form of muscular dystrophy, for most of his adult life. (read complete story)

So glad to have a personality come forward and speak out for FSHD - increasing the public's awareness of this condition can only help in attracting new researchers to work on FSH and new donors to support their work.

Additionally, his leadership may help inspire others with FSH (and their loved ones and friends) to take action as well - seeing Chris's impact may show others what is possible.

I truly hope others will come forward.........

The Ways to Cope With (FSHD) Facioscapulohumeral Muscular Dystrophy : Progressive Muscular Dystrophy

2011-07-19T17:53:00.000-07:00

Ways to Cope With (FSHD) Facioscapulohumeral Muscular Dystrophy : Progressive Muscular Dystrophy

Helpful post regarding the care of your eyes, pain management, etc. for those living with FSHD.

FSHD Foundation - Netherlands

2011-07-17T10:48:00.000-07:00

The great big work and life juggle - Business of Life - livemint.com

Van der Graaf’s oldest son, Bart, was diagnosed with FSHD (facioscapulohumeral form of muscular dystrophy) in 1992, and that changed his life forever. He realized he had to establish a balance between his personal and professional life. Along with his wife, Renée, Van der Graaf founded the FSHD Foundation. In 2008, at the pinnacle of his career, he decided to take early retirement from Unilever and devote his time to the foundation.

Read more about Kees Van der Graaf, his work, his family's effort to fund FSHD research and their work toward finding a treatment or cure for their affected son.

Inspirational story of one family's dedication - the "power of one."

NETS: Chris Carrino Foundation

2011-07-14T19:15:00.000-07:00

NETS: Chris Carrino Foundation Dinner Dance Q&A

Stem cell foundation for muscular dystrophy

2011-07-14T19:06:00.000-07:00

Health News - Stem cell foundation for muscular dystrophy treatment

Seeking Donations - Eager Recipient looking for Help!

2011-06-30T16:55:00.000-07:00

Wondering if anyone out there that may read my blog might have ideas about how best to procure items for an auction. I have done this now for over 7 years and every year it presents a huge obstacle. I am dedicated and determined to raise money needed for FSH research yet, I find asking for help/donations continues to be hard. I feel we do a great job of showing off the donor's items (such as artwork, jewelry, pottery, etc) and we put the donor's website's out there on our site and on all our written literature.... not sure if this is "giving back" enough to inspire spontaneous giving.
I wonder how other groups do this? in person contacts? emails? letters?
Feed back & ideas welcomed. (Donations greeted with great enthusiasm!!)

FSHD - Overview

2011-06-24T20:02:00.000-07:00

Facioscapulohumeral Muscular Dystrophy - GeneReviews - NCBI Bookshelf

Facioscapulohumeral Muscular Dystrophy

FSH Muscular Dystrophy

RichardJLF Lemmers, PhD

Department of Human and Clinical Genetics
Leiden University Medical Center

R.J.L.F.Lemmers@lumc.nl

SilvereM van der Maarel, MD

Department of Human and Clinical Genetics
Leiden University Medical Center

S.M.Maarel@lumc.nl

Excellent reference written by expert researchers in the field of FSH research.

GiveBig for FSHD research - June 23rd

2011-06-22T18:24:00.000-07:00

Dear Friends,

On June 23^rd there is an exciting opportunity to put more "muscle" in your donation to Friends of FSH Research.

Give BIG is a community-wide giving challenge created by

The Seattle Foundation that will increase the size of your

donations to us.

This one-day, online charitable giving event will rally together our community on behalf of the amazing nonprofit organizations in King County - this includes Friends of FSH Research!

GiveBIG will grow your generosity in several ways:

· Grow your gift! The Seattle Foundation and local businesses will match a share of every contribution made through The Seattle Foundation's online Giving Center between 7 a.m. and midnight on June 23.

· Win a Golden Ticket! During the day, if your donation is selected at random, Friends of FSH Research will receive an additional $1,000 from GiveBIG's sponsors.

Your gift will help us support critical Facioscapulohumeral Muscular Dystrophy (FSH) research. Help us make a treatment or cure to this debilitating condition a reality now!

Mark your calendar now! Make your donation to Friends of FSH Research between 7 a.m. and midnight on Thursday June 23 through our page in The Seattle Foundation's Giving Center.

Help us make the most of GiveBIG! Here are a few more things you can do in addition to making a generous gift:

1. Mark your calendar today, so you don't forget to make a gift on June 23!

2. RSVP for GiveBIG on Facebook

3. Rally your friends to support Friends of FSH Research on June 23! Email, Facebook, Twitter & phone calls are great ways to spread the word and help us take advantage of GiveBIG.

4. Be sure to share the link to our profile

Thank you in advance for Giving Big. With your help will truly be able to make a difference to those affected by FSH Muscular Dystrophy!!

Sincerely,

Terry Colella

PS: You can learn more about GiveBIG online atwww.seattlefoundation.org/GiveBIG.

Expression Profiling of FSHD-1 and FSHD-2 Cells during Myogenic Differentiation

2011-06-14T13:46:00.000-07:00

Recent Report from Italy - FSHD research News

Global gene-expression profiles of myoblasts from FSHD-1 and FSHD-2 patients and healthy controls in the context of myogenic differentiation are discussed.

Kirkland mother fights to fund research, find cure for son’s degenerative muscle disease

2011-02-14T12:05:00.000-08:00

Kirkland mother fights to fund research, find cure for son’s degenerative muscle disease

On a recent afternoon, the mother-of-four walks through the downstairs of her Kirkland home that is packed with dozens of acrylic and oil paintings, wine bottles, granite rock vases, French serving platters, gift baskets, books and more. Terry’s downstairs has become a storage for items up for bid at her annual auctions she hosts to fund research for Brian’s degenerative muscular disease, FSHD (Facioscapulohumeral Muscular Dystrophy). This year marks the 7th Annual “FiSHing for a Cure Gala” dinner and auction, which will be held on Saturday, Jan. 29 at the Bellevue Hyatt. To date, the auctions have raised more than $1.2 million that has funded groundbreaking research for the disease.

(read entire story at Kirkland Reporter)

FSHD - 1st known human disease caused by unique circumstance

2011-02-05T09:02:00.000-08:00

Trends Mol Med. 2011 Jan 31. [Epub ahead of print]

Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence.

van der Maarel SM, Tawil R, Tapscott SJ.

Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, Netherlands.

Abstract

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) has an unusual pathogenic mechanism. FSHD is caused by deletion of a subset of D4Z4 macrosatellite repeat units in the subtelomere of chromosome 4q. Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. In FSHD, the combination of inefficient chromatin silencing of the D4Z4 repeat and polymorphisms on the FSHD-permissive alleles that stabilize the DUX4 mRNAs emanating from the repeat result in inappropriate DUX4 protein expression in muscle cells. FSHD is thereby the first example of a human disease caused by the inefficient repression of a retrogene in a macrosatellite repeat array.

NIH - Update FSH Research

2011-02-01T21:44:00.000-08:00

Spotlight on Research 2011

January 2011

Genetic Discovery Improves Understanding of FSH Muscular Dystrophy Cause

A new study supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has found that two separate genetic arrangements – both on chromosome 4 – are needed to start the disease process in facioscapulohumeral muscular dystrophy (FSHD), one of the most common forms of muscular dystrophy. The finding brings scientists a step closer to understanding the cause of FSHD, knowledge that would allow researchers to begin designing strategies that could eventually lead to treatments.

The study’s international team of investigators, including NIAMS-supported scientist Stephen Tapscott, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle, discovered that a repeating DNA unit containing a gene called DUX4 interacts with adjacent genetic variations to determine whether a person will have FSHD, which causes progressive muscle wasting in the upper body.

In the early 1990s, scientists found that FSHD is associated with a shortened DNA sequence at the end of chromosome 4, called a tandem repeat array. Normally, that region of the chromosome contains 10 to 100 repeating units of DNA. They found in most people with FSHD the array is smaller, with fewer than 10 repeats. Within each repeating unit is the DUX4 gene, which encodes a protein that harms muscle cells. Later research, however, showed that this genetic variation alone could not cause FSHD – something else was needed to trigger the disease’s muscle damage. The new research, reported in the journal Science, demonstrates that the smaller array only causes FSHD if there is an additional DNA mutation in the same region of chromosome 4 that allows DUX4’s RNA to stabilize and the protein to accumulate to disease-causing levels.

People with FSHD have chromosome variations that add a trailing segment called a poly(A) tail to the RNA. With the poly(A) tail, the RNA is more stable and accumulates to detectable levels. Previous studies have shown that expression of the DUX4 gene in muscle cells causes defects in cellular growth, development and the ability to maintain internal stability that are consistent. In a subsequent publication, Dr. Tapscott’s research group demonstrated a full-length DUX4 RNA with a poly(A) tail expressed in skeletal muscle from FSHD patients, but not in muscle from control subjects.

While further research is needed to confirm and better understand the implications of their findings, the scientists say that their results may make it easier for doctors to diagnose FSHD in people with muscular dystrophy symptoms. In addition, for those in affected families who have not yet experienced symptoms, the results will help predict who may develop the disease. The study also has important implications for treatment. Presently, treatment for FSHD is limited to physical therapy, orthopaedic procedures and drugs that may help with specific symptoms in some patients. Although there are no treatments for the progressive muscle weakness and wasting characteristic of FSHD, the new findings point to potential targets for treating the disease in novel ways that address the causes.

Support for the study was provided by a number of other organizations, including the National Institute of Neurological Disorders and Stroke (NINDS), the FSH Society, the Fields Center for FSHD and Neuromuscular Research, the Pacific Northwest Friends of FSH Research and the Muscular Dystrophy Association.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website athttp://www.niams.nih.gov.

###

Lemmers RJ, van der Vliet PJ, Klooster R, Sacconi S, Camaño P, Dauwerse JG, Snider L, Straasheijm KR, van Ommen GJ, Padberg GW, Miller DG, Tapscott SJ, Tawil R, Frants RR, van der Maarel SM. A unifying genetic model for facioscapulohumeral muscular dystrophy. Science. 2010 Sep 24;329(5999):1650-3.

Major breakthrough in muscular dystrophy research

2010-12-16T08:57:00.000-08:00

Major breakthrough in muscular dystrophy research

It’s often said in research circles that many pairs of eyes are better than just one set when it comes to looking at complex problems.

And at the Hutchinson Center, that kind of collaboration reaches across the globe—often leading to groundbreaking results. Such is the case with the latest news on muscular dystrophy, a disease that has vexed the scientific community for decades.

Researchers have known for 20 years that a genetic mutation is present in people with a common form of muscular dystrophy known as facioscapulohumeral dystrophy, or FSHD, a condition characterized by progressive wasting of muscles in the upper body.

People affected by FSHD share a gene called DUX4 that produces a protein toxic to muscle cells. However, researchers had not been able to explain what caused DUX4 to mutate and create the toxic protein.

Now, they think they have found the key that turns the process on. This summer, an international team—with a Hutchinson Center researcher in a pivotal role—identified a DNA sequence that causes DUX4 to be more active. They now believe that two distinct genetic changes on chromosome 4 must be present to cause FSHD.

“In contrast to most genetic diseases, knowledge of the genetic mutation did not explain the cause of the disease,” said Dr. Stephen Tapscott, an expert in neurogenetics and neuromuscular disease at the Hutchinson Center, and one of the co-authors of the study.

Thanks to these findings, researchers hope it will become easier to diagnose the disease and predict in people showing no symptoms, who will develop it. Currently, FSHD affects 300,000 people worldwide. The latest research also is likely to open the door to new therapies.

“The progress was made possible by an unusual degree of collaboration and data-sharing among the individual groups,” said Tapscott, who was one of several researchers who participated in the study.

(note: Friends of FSH Research launched Dr. Tapscott and the work at Fred Hutch through a pilot grant given in 2006 and other supportive funding through 2010)

FSHD: copy number variations on the theme of muscular dystrophy — JCB

2010-12-14T10:48:00.000-08:00

FSHD: Copy Number Variations on the Theme of Muscular Dystrophy

JCB Home, Dec. 13

In humans, copy number variations (CNVs) are a common source of phenotypic diversity and disease susceptibility. Facioscapulohumeral muscular dystrophy (FSHD) is an important genetic disease caused by CNVs. It is an autosomal-dominant myopathy caused by a reduction in the copy number of the D4Z4 macrosatellite repeat located at chromosome 4q35. Interestingly, the reduction of D4Z4 copy number is not sufficient by itself to cause FSHD. A number of epigenetic events appear to affect the severity of the disease, its rate of progression, and the distribution of muscle weakness. Indeed, recent findings suggest that virtually all levels of epigenetic regulation, from DNA methylation to higher order chromosomal architecture, are altered at the disease locus, causing the de-regulation of 4q35 gene expression and ultimately FSHD.

(click on title link to read entire report)

Conclusions

Recent studies suggest that copy number variations (CNVs) are important for human phenotypic diversity and disease susceptibility. DNA repeats account for 55% of the human genome and a significant fraction of CNVs.

FSHD is an important pathology caused by CNVs of D4Z4 repeats. It is an extremely complicated and fascinating disease, and research into this topic is revealing much about the functional organization of our genome.

An increasing amount of evidence suggests that the 4q35 macrosatellite repeat D4Z4 plays a crucial role in the chromosomal organization of the FSHD region. There is a general consensus that the D4Z4 deletion in FSHD leads to epigenetic alterations that affect the expression profiles of genes within the FSHD region. Unfortunately, despite considerable effort, almost 20 years after the identification of the genetic defect underlying the disease, the causative FSHD gene(s) remains unknown, and no effective treatments for FSHD are currently available.

The heterogeneity in disease manifestation probably reflects heterogeneity in gene expression in FSHD. An interesting possibility, therefore, is that the complexity of FSHD could be explained by considering it to be a contiguous gene syndrome, where the epigenetic alteration of DUX4, FRG1, and other potential genes collaborate to determine the final phenotype. Finally, because DUX4 behaves as a transcriptional activator (Dixit et al., 2007), it could play a direct role in transcriptional overexpression of the other 4q35 genes, providing a unifying model for the molecular mechanism of the disease.

Ryan Levinson - Can’t choose what happens to you, only how you respond to it.”

2010-12-09T15:27:00.000-08:00

Read article about Ryan Levison - FSHD Athlete

New FSHD Findings - Summary

2010-11-24T10:15:00.000-08:00

(This is a nice summary of recent research findings - from the UK Muscular dystrophy newsletter - you can read more about this work, and the work done by researchers funded by Friends of FSH Research on our website)

Monday 22 November 2010

New research increases understanding of facioscapulohumeral muscular dystrophy.

An international group of scientists has shed further light on the molecular mechanism that causes facioscapulohumeral muscular dystrophy (FSH). Recent research has provided evidence that the piece of that is changed in people with FSH contains a called DUX4, the function of which is so far unknown. The results of this new research provide evidence that the DUX4 gene can produce different versions of DUX4 protein and that the deletion in patients with FSH leads to the production of a version that is toxic for muscle cells. These important findings will be vital to bring scientists closer to developing a treatment.

FSH is caused by changes to a region of DNA on 4 called D4Z4 that has the same piece of DNA code repeated many times. In healthy individuals the number of repeats varies between 11 and 100. People with FSH have less than 11 repeats. Recent research demonstrated that the repeated section of DNA contains a gene called DUX4. The reduction in the number of repeats on D4Z4 to less than 11 changes the way this piece of DNA is folded (this is known as the chromatin structure). This exposes the DNA code to be read by the cell, like opening a book. They also showed that an activation signal also needs to be present next to the DUX4 gene. In other words, the book needs to be open and the light switched on before you can read it. Read more about these previous results.
But this is not the whole story and this new research builds on these previous findings to further clarify the mechanism causing FSH.

What does the research show?

The researchers analysed tissue samples to find out more about the that is produced from the instructions in the DUX4 gene. They found that the DUX4 protein was made in two forms - a full-length and a shortened version. The full-length protein could not be found in the muscles of people unaffected by FSH, instead the shorter version of the protein was found. Of the tissues they examined, the full-length version was only present in testes. However, muscle samples from people with FSH were found to be producing the full length DUX4 protein. It should be noted that in people with FSH only a very small proportion of muscle cells produce the longer version of the protein.
These results suggest that muscle cells actively read the DUX4 gene but the protein is processed differently in people with FSH. This leads to the production of the full-length version that is not found in the muscle cells of people unaffected with FSH. It is thought that the way the DNA is folded may be determining this. In healthy cells the DNA is more tightly coiled and this may be influencing the cell to "cut out" parts of the DUX4 protein to create the shortened version. The DNA in the FSH muscle is much more loosely folded, due to the smaller number of repeats, and so this signal to "cut out" part of the protein is missing.
The researchers also analysed "induced pluripotent " (iPS). These are made in the laboratory by reprogramming cells that already have a dedicated function, such as skin cells, so that they become stem cells. iPS cells are a useful tool for stem cell research and can be used to model disease processes. When researchers looked at iPS cells made from skin they found that they produced the full-length DUX4 protein which did not seem to be toxic for this cell type.
The researchers have suggested that the fact that the full-length version of the DUX4 protein is produced only in stem cells and testicular tissue might mean that it has a possible role during early development. In adult tissue, especially in muscle, the production of the full-length protein is switched off and the shorter version is produced. The changes in the DNA in people with FSH somehow have the effect that this switch is not happening. The muscle cells keep on making the full-length DUX4 protein that becomes toxic to the cells, inducing muscle damage.

What does this mean for patients?

This research represents a big step forward in our understanding of what causes FSH, something that has prevented scientists moving forward to develop potential therapies. These new results will allow researchers to further clarify the role of the DUX4 gene and protein in the development of the condition.
It is still not fully understood what the function the DUX4 protein is and why the full-length DUX4 protein appears to be toxic to the muscle and researchers will continue to investigate this. This current piece of research and the other recent findings about FSH have however, highlighted a target which researchers can now take advantage of to potentially start developing a therapy for this condition.

Inflammatory Role - Impacting FSHD Muscle Cells

2010-11-13T09:14:00.000-08:00

J Clin Immunol. 2010 Nov 10. [Epub ahead of print]

CD8(+) T Cells in Facioscapulohumeral Muscular Dystrophy Patients with Inflammatory Features at Muscle MRI.

Frisullo G, Frusciante R, Nociti V, Tasca G, Renna R, Iorio R, Patanella AK, Iannaccone E, Marti A, Rossi M, Bianco A, Monforte M, Tonali PA, Mirabella M, Batocchi AP, Ricci E.

Institute of Neurology, Department of Neurosciences, Catholic University of Rome, largo Gemelli 8, 00168, Rome, Italy.

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8(+) T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8(+)pSTAT1(+), CD8(+)T-bet(+) T cells and CD14(+)pSTAT1(+), CD14(+)T-bet(+) cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8(+)pSTAT1(+), CD8(+)T-bet(+) and CD14(+)pSTAT1(+) cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8(+) T cells, may favour FSHD progression by promoting active phases of muscle inflammation.

PMID: 21063901 [PubMed - as supplied by publisher]

Dave Matthews & Tim Reynolds - Singing for Charity

2010-11-07T13:35:00.000-08:00

Dave Matthews and Tim Reynolds will perform two unprecedented special benefit concerts on December 6th and 7th at Seattle’s McCaw Hall. One hundred percent of the proceeds from these two shows will benefit charities selected by each ticket purchaser.

Here’s how this works:

For each ticket you purchase for $135 for either show, you will receive a unique code worth $150 that you may use to direct a donation to any charity of your choosing on JustGive.org (a nonprofit organization that connects people to over 1.8 million charities).

Pacific Northwest Friends of FSH Research
Kirkland, WA 98033
Tax ID: 86-1108537

Have fun giving with your fellow concertgoers. Consider making a collective impact by encouraging your neighbors and friends to all choose Friends of FSH Research!

Your directed donation is funded by Dave Matthews and a generous supporter.

100% of the proceeds will be donated the charity selected by the ticket purchasers.

Bottom line… See a great show while helping fund FSH Research! THANKS!

Accessibility on Melbourne's trams - Thanks Ray!

2010-11-06T10:49:00.001-07:00

Friends of FSH Research - An international research consortium shows that FSHD muscle nuclei are poised for expression of the toxic DUX4 protein

2010-11-02T22:20:00.000-07:00

Friends of FSH Research - An international research consortium shows that FSHD muscle nuclei are poised for expression of the toxic DUX4 protein

Dr. Silvère van der Maarel

After their recent publication in Science, the same international research collaboration that includes research groups funded by the Friends of FSH Research has made further advancements in our understanding of the molecular cause of facioscapulohumeral dystrophy (FSHD). While their earlier work reported in Science provided genetic evidence that expression and stabilization of DUX4 is critically important for the development of FSHD, the recent report in PLoS Genetics provides an answer as to how a gene expressed at such low concentrations can be toxic to muscle. Low expression of DUX4 can either mean that all muscle nuclei express tiny amounts of the toxic DUX4 protein or that only few out of many nuclei express high levels of DUX4. In this report, the scientists provide compelling evidence for the latter scenario. This finding is important as it provides a model in which occasional bursts of DUX4 in muscle of patients with FSHD can explain the progressive nature of this disease. It also provides a clear target for the design of therapeutics for FSHD.

(read complete article on our website - Please donate to help us push this work toward a cure, thank you)

FSHD: A Repeat Contraction Disease Finally Ready to Expand

2010-10-31T10:26:00.000-07:00

PLoS Genetics: FSHD: A Repeat Contraction Disease Finally Ready to Expand (Our Understanding of Its Pathogenesis)

Christopher E. Pearson¹^,²^*

1 Program of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, 2 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

Facioscapulohumeral muscular dystrophy (FSHD), was one of the first diseases shown to be caused by an unstable repeat in the early 1990s along with spinal and bulbar muscular atrophy (SBMA), myotonic dystrophy (DM1), and fragile X mental retardation (FRAXA), where the latter three are caused by genetically expanding trinucleotide repeats [1]. However, FSHD differs considerably from the trinuclotide repeat diseases, as it is caused by a contraction of a macrosatellite (D4Z4 repeat, 3.3 kb/unit). Moreover, far less is understood about the pathogenic mechanism for FSHD, relative to SBMA, DM1, and FRAXA. This is not due to a shortage of experimental efforts, plausible hypotheses, or collaborative efforts towards understanding FSHD [2], [3]. The elucidation of FSHD is hampered by the size of the unstable repeat, its sequence complexity, the number of repeat units, and the presence of the repeat on Chromosomes 4 and 10, making analysis technically difficult. The difficulty is compounded further by the absence of an obvious gene, transcript, or protein in the unstable or proximal region; in fact, the D4Z4 repeats have been referred to as “junk” DNA or are thought to be a pseudogene, at best. As a result, FSHD has proved to be one of the most complex and challenging genetic diseases to even a glimpse an underlying pathogenic cause for FSHD. Several recent papers, including one in this issue of PLoS Genetics [4], have made significant advances that now permit us to expand our understanding of FSHD pathogenesis, a repeat contraction disease.

(Click link to read entire article)

Uncovering the Cause of a Common Form of Muscular Dystrophy: Research Team Makes Second Critical Advance | Science Magazine News

2010-10-28T22:03:00.000-07:00

In August 2010 the group published a landmark study that established a new and unifying model for the cause of FSHD. The current work, published Oct. 28 in PLoS Genetics, shows that the disease is caused by the inefficient suppression of a gene that is normally expressed only in early development. The work will lead to new approaches for therapy and new insights into human evolution.

The disease-causing gene, called DUX4, previously had been thought to be a completely inactive gene in humans. DUX4 belongs to a special class of genes called retrogenes, which usually represent unused byproducts of evolution that have no remaining biological function, sometimes called "dead genes."

In contrast, the researchers discovered that the DUX4 protein is abundantly expressed in human germ-line cells, the cells that form the sperm and eggs, which indicates a necessary function early in development. Normally, the DUX4 gene is suppressed in all other cells of the body. However, the mutation that causes FSHD makes this suppression less efficient.

"The result is that the DUX4 gene occasionally escapes the inefficient suppression and is expressed in some muscle cells, similar to the Old Faithfull geyser that is usually off but occasionally releases a burst of water," said corresponding author Stephen Tapscott, M.D., Ph.D., a member of the Hutchinson Center's Human Biology Division. "The occasional 'bursts' of DUX4 are thought to be toxic to the muscle cells, which leads to muscle cell death and the muscular dystrophy."

Tapscott led the study in collaboration with Daniel Miller, M.D., Ph.D., at the University of Washington, and co-authors Silvere van der Maarel, Ph.D., and Rabi Tawil, M.D., at Leiden University Medical Center and the Fields Center for FSHD and Neuromuscular Research at the University of Rochester, respectively.

Previously, these same investigators had shown that the reason some people are protected from getting FSHD is that they have mutations in a region of DNA that is necessary to stabilize the DUX4 gene product. These new findings confirm the role of the DUX4 protein in FSHD and reveal a new mechanism of human disease caused by the inefficient suppression of a retrogene that has a role in early development. These findings will provide a focus for future development of therapies for FSHD.
There are broader implications of the new research for understanding human evolution as well. Maintenance of a functional retrogene in humans indicates that it provided some selective advantage during evolution.

"Since FSHD is characterized by excessively weak upper extremity muscles and facial muscles, we speculate that the DUX4 retrogene might have a normal role in causing the weaker and more expressive facial muscles in humans compared to non-human primates," Tapscott said. "If this suggestion is correct, it means that FSHD is caused by increasing the normal role of DUX4 and causing a more extreme weakness of facial and upper extremity muscles. It also means that all humans have a little bit of FSHD and that this contributes to the evolution of these muscles."

The researchers have an ongoing collaboration through a Hutchinson Center-based National Institutes of Health FSHD Program Project Grant, of which Tapscott is principal investigator, and through the Fields Center for FSHD and Neuromuscular Research, of which Tawil is the director.

"The progress was made possible by an unusual degree of collaboration and data-sharing among the individual groups," Tapscott said.

Grants from the NIAMS and NINDS sections of the National Institutes of Health, the Friends of FSH Research, the Shaw Family Foundation and the Muscular Dystrophy Association also supported the work of Tapscott and colleagues at the Hutchinson Center.

Other funding for this study came from the Fields Center, the Netherlands Organization for Scientific Research, the Netherlands Genomic Initiative, a Marjorie Bronfman Fellowship grant from the FSH Society, the Centro Investigacion Biomedica en Red para Enfermedades Neurodegenerativas, the Basque Government and the Instituto Carlos III, ILUNDAIN Fundazioa.

Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.
Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Fred Hutchinson Cancer Research Center.

Uncovering the cause of a common form of muscular dystrophy

2010-10-28T15:08:00.000-07:00

Research team makes second critical advance

SEATTLE—Oct. 28, 2010

An international team of researchers led by an investigator from Fred Hutchinson Cancer Research Center has made a second critical advance in determining the cause of a common form of muscular dystrophy known as facioscapulohumeral dystrophy, or FSHD.

In August 2010 the group published a landmark study that established a new and unifying model for the cause of FSHD. The current work, published Oct. 28 in PLoS Genetics, shows that the disease is caused by the inefficient suppression of a gene that is normally expressed only in early development. The work will lead to new approaches for therapy and new insights into human evolution.

The disease-causing gene, called DUX4, previously had been thought to be a completely inactive gene in humans. DUX4 belongs to a special class of genes called retrogenes, which usually represent unused byproducts of evolution that have no remaining biological function, sometimes called “dead genes.”

In contrast, the researchers discovered that the DUX4 protein is abundantly expressed in human germ-line cells, the cells that form the sperm and eggs, which indicates a necessary function early in development. Normally, the DUX4 gene is suppressed in all other cells of the body. However, the mutation that causes FSHD makes this suppression less efficient.

“The result is that the DUX4 gene occasionally escapes the inefficient suppression and is expressed in some muscle cells, similar to the Old Faithfull geyser that is usually off but occasionally releases a burst of water,” said corresponding author Stephen Tapscott, M.D., Ph.D., a member of the Hutchinson Center’s Human Biology Division. “The occasional ‘bursts’ of DUX4 are thought to be toxic to the muscle cells, which leads to muscle cell death and the muscular dystrophy.”

Tapscott led the study in collaboration with Daniel Miller, M.D., Ph.D., at the University of Washington, and co-authors Silvere van der Maarel, Ph.D., and Rabi Tawil, M.D., at Leiden University Medical Center and the Fields Center for FSHD and Neuromuscular Research at the University of Rochester, respectively.

Previously, these same investigators had shown that the reason some people are protected from getting FSHD is that they have mutations in a region of DNA that is necessary to stabilize the DUX4 gene product. These new findings confirm the role of the DUX4 protein in FSHD and reveal a new mechanism of human disease caused by the inefficient suppression of a retrogene that has a role in early development. These findings will provide a focus for future development of therapies for FSHD.

There are broader implications of the new research for understanding human evolution as well. Maintenance of a functional retrogene in humans indicates that it provided some selective advantage during evolution.

“Since FSHD is characterized by excessively weak upper extremity muscles and facial muscles, we speculate that the DUX4 retrogene might have a normal role in causing the weaker and more expressive facial muscles in humans compared to non-human primates,” Tapscott said. “If this suggestion is correct, it means that FSHD is caused by increasing the normal role of DUX4 and causing a more extreme weakness of facial and upper extremity muscles. It also means that all humans have a little bit of FSHD and that this contributes to the evolution of these muscles.”

The researchers have an ongoing collaboration through a Hutchinson Center-based National Institutes of Health FSHD Program Project Grant, of which Tapscott is principal investigator and through the Fields Center for FSHD and Neuromuscular Research, of which Tawil is the director.

“The progress was made possible by an unusual degree of collaboration and data-sharing among the individual groups,” Tapscott said.
Grants from the NIAMS and NINDS sections of the National Institutes of Health, the Friends of FSH Research, the Shaw Family Foundation and the Muscular Dystrophy Association also supported the work of Tapscott and colleagues at the Hutchinson Center.

Other funding for this study came from the Fields Center, the Netherlands Organization for Scientific Research, the Netherlands Genomic Initiative, a Marjorie Bronfman Fellowship grant from the FSH Society, the Centro Investigacion Biomedica en Red para Enfermedades Neurodegenerativas, the Basque Government and the Instituto Carlos III, ILUNDAIN Fundazioa.

Note for media only: To obtain a copy of the PLoS Genetics paper, “Facioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene,” or to arrange an interview with Tapscott, please contact Kristen Woodward in Hutchinson Center media relations at 206-667-5095 or kwoodwar@fhcrc.org.

###

Kristen Woodward
Fred Hutchinson Cancer Research Center
(206) 667-5095
kwoodwar@fhcrc.org

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FSHD Muscular Dystrophy - Documentary

2010-10-26T14:12:00.000-07:00

The challenge of unraveling the genetics of FSHD

2010-10-26T13:53:00.000-07:00

Preliminary ACE-031 Results

2010-10-13T18:15:00.000-07:00

Acceleron Presents Preliminary ACE-031 Results from a Phase 1 Multiple Ascending Dose Study in Healthy Volunteers

Acceleron Pharma, Inc., a biopharmaceutical company developing novel therapeutics that modulate the growth of cells and tissues including muscle, bone, fat, red blood cells and the vasculature, today announced preliminary results from a Phase 1b study to assess the safety, tolerability and pharmacodynamic (PD) activity of ACE-031 following multiple ascending doses in healthy postmenopausal volunteers. ACE-031 is an investigational protein therapeutic designed to build muscle and increase strength by blocking proteins that inhibit muscle growth. In the trial, ACE-031 was generally well-tolerated with rapid and sustained effects on muscle, bone and fat. Preliminary results from this randomized, placebo-controlled study were presented at the 15^th International Congress of the World Muscle Society in Kumamoto, Japan.

Read more: http://www.kansascity.com/2010/10/13/2307913/acceleron-presents-preliminary.html#ixzz12I8Xufqg

A Unifying Genetic Model for FSHD - Review

2010-10-06T10:26:00.000-07:00

Faculty of 1000 Biology |
A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy.
By Dr. Jane Hewitt

This publication gives significant insight into the fascinating and unique molecular mechanism of facioscapulohumeral muscular dystrophy (FSHD). The causative mutation has been known for almost 20 years to be a deletion in a tandem DNA array (D4Z4) encoding a putative homeodomain protein (DUX4), but why the deletion results in FSHD has been unclear and hotly debated. D4Z4 deletions only cause FSHD if they occur on particular 4q haplotypes that are termed permissive. Now, Lemmers et al., using a combination of high resolution haplotyping and analysing patients with atypical but informative genetic architectures, provide a plausible and intriguing model for FSHD. They show that D4Z4 deletions allow inappropriate generation of a transcript (DUX4) from the distal D4Z4 repeat that utilises a non-canonical polyA signal in an adjacent stretch of beta-satellite DNA, stabilising the mRNA.

The FSHD mutation was first identified in 1992 as a deletion within the D4Z4 tandem DNA array at chromosome 4q35 {1}. This polymorphic array contains 12-150 copies of a 3.3kb DNA repeat in unaffected individuals; in FSHD patients, the number of repeat units is reduced to about 10 or fewer. Although the potential for this array to encode a homeodomain protein was recognised almost immediately {2}, it proved difficult to find evidence that a transcript or protein was produced. Consequently, many researchers proposed that the D4Z4 deletions altered the chromatin structure of this region, affecting the expression of genes proximal to the array. Although there were some data that supported this position effect model, many other studies failed to replicate these findings. Recently, several groups identified transcriptional activity from D4Z4 {3,4} and the DUX4 open reading frame was shown to be evolutionarily conserved {5}; D4Z4 has for several years been known not to be junk DNA or a dead gene. Together with data showing that only some 4q haplotypes are permissive for the disease {6}, these findings shifted focus back to a direct role for the D4Z4 repeat in FSHD. Epigenetic changes in D4Z4 chromatin that were specific for FSHD were recently identified {7}. Here, Lemmers et al. provide a model that is consistent with all these previous studies on D4Z4. Like any good paper, this one raises further questions. Lemmers et al. previously reported that one 4q haplotype (termed 4qA166) is non-permissive for FSHD {6}. Here, they do not report whether the polyA signal is absent in this non-permissive haplotype. A subset of FSHD patients (termed phenotypic FSHD or FSHD2) do not have D4Z4 deletions but do show similar epigenetic changes within the array. It will be important to test whether these patients also show inappropriate activation of DUX4 mRNA. Finally, this polyadenylation signal is not essential for normal DUX4 function since approximately 25% of the population is homozygous for 4qB haplotypes that lack this sequence. Therefore, the relationship between normal DUX4 function and FSHD remains to be resolved. NB - Jane Hewitt is an author on refs {1,2,5}.

References: {1} Wijmenga et al. Nature Genet 1992, 2:26-30 [PMID:1363881]. {2} Hewitt et al. Hum Mol Genet 1994, 3:1287-95 [PMID:7987304]. {3} Dixit et al. Proc Natl Acad Sci USA 2007, 104:18157-62 [PMID:17984056]. {4} Snider et al. Hum Mol Genet 2009, 18:2414-30 [PMID:19359275]. {5} Clapp et al. Am J Hum Genet 2007, 81:264-79 [PMID:17668377]. {6} Lemmers et al. Am J Hum Genet 2007, 81:884-94 [PMID:17924332]. {7} Zeng et al. PLoS Genet 2009, 5:e1000559 [PMID:19593370].

Multi-National Research - Making Strides for FSHD Research

2010-10-05T11:26:00.000-07:00

Two genetic changes needed to cause FSHD

Facioscapulohumeral muscular dystrophy (FSHD) requires the presence of not one but two genetic changes, both on chromosome 4, MDA-supported scientists have found.
MDA grantee Silvère van der Maarel at Leiden (Netherlands) University Medical Center coordinated the multinational study team, which announced its findings online Aug. 19, 2010, in the journal Science.

Two genetic changes — a contracted segment of DNA on chromosome 4, and a "permissive" signal near it on the same chromosome — are necessary to complete the FSHD puzzle.

The investigators found that two genetic requirements, located near each other on the tip of chromosome 4, must be combined for FSHD symptoms to appear. One requirement is a deletion of some of the DNA in a region of chromosome 4 called D4Z4. Its contribution to FSHD has been recognized for many years. The second requirement, newly recognized, is a particular variant of DNA further toward the tip of chromosome 4 than the D4Z4 region.

The variant contains a “polyadenylation” signal, which stabilizes otherwise fragile genetic instructions called RNA transcripts, after they’re synthesized from DNA (genes).

The presence of a polyadenylation signal makes it more likely that genetic instructions will stick around long enough to be translated into proteins, the final product of DNA and RNA instructions. In this case, the signal appears to make it possible for one or more potentially toxic proteins to be produced.

More than 300 people with FSHD and more than 2,000 people without the disease were studied. All the people with FSHD had a contracted D4Z4 region on chromosome 4 and at least one of three “permissive” DNA sequences further out toward the tip of the same chromosome.

Among the more than 2,000 people without any FSHD symptoms that the investigators studied, some had contracted D4Z4 regions on chromosome 4. However, they all had “nonpermissive” signals further out on the chromosome.
Without a “permissive” polyadenylation signal, the researchers believe, genetic instructions (RNA) from the D4Z4 region don’t last long enough to cause muscle-cell damage.

The new findings will make it easier to diagnose FSHD in someone with symptoms and predict who will develop the disease among those without symptoms.
Once the identities of the toxic proteins or RNA instructions are established, therapeutic strategies to block them could potentially be developed.

(Part of the multi-national team responsible for these recent findings include Friends of FSH Research supported Seattle researchers - Thanks to everyone for your donations that made this work possible)

Running for FSHD Research

2010-09-28T11:50:00.000-07:00

Invest in Others - BOSTON, July 28 /PRNewswire/ --

Runner - Andrew Prentice - Runs For FSH Research

BOSTON, July 28 /PRNewswire/ -- The Invest in Others Charitable Foundation, Inc., a public charity that supports the philanthropic and volunteer efforts of financial advisors across the country, today announced it has contributed $30,000 to Pine Street Inn through its Second Annual 5K Run/Walk event in Boston on Wednesday, July 28, 2010. Founded and based in Boston, Pine Street Inn is a charity committed to ending homelessness in the organization's home town. The donation will be directed towards Pine Street Inn's new Hartford Street Project, a 16-unit supportive housing program for homeless U.S. veterans that Pine Street Inn is preparing to open in the fall of 2010.

Following the Run/Walk, Invest in Others also awarded the top three male and female financial advisor finishers with a generous donation to the charity of their choice. This year's honorees included:

Andrew Prentice of Bliss Investments in Olympia, WA; first place male financial advisor; benefiting Friends of FSH Research

New Report Regarding Fascioscapulohumeral Dystrophy

2010-09-19T11:07:00.000-07:00

Fascioscapulohumeral Dyst... : Neurology Today (to see entire article)

Neurology Today:

16 September 2010 - Volume 10 - Issue 18 - p 15

Although questions remain, the discovery, reported online in Science on Aug. 19, points the way toward an effective treatment for FSHD, which produces progressive wasting of muscles in the upper body.

“I don't think the importance of this can be over-emphasized,” said John Porter, PhD, program director of Neuromuscular Disease at the Neurogenetics Cluster and the NINDS Office of Translational Research, who was not involved with the study. “Without a mechanistic model that provides a hypothesis about the pathogenesis of a disease, researchers have difficulty getting grants. Grant applications have to be supported by a conceptual framework, and this provides a huge building block.”

(read entire report at Neurology Today)

September is Muscular Dystrophy Awareness Month

2010-09-01T08:17:00.000-07:00

TORONTO, ONTARIO-- Sept. 1, 2010 - Keith Martin is a typical young adult in many ways: he's an avid Habs fan, and enjoys travelling and hanging out with friends. Keith is also a champion.

In 2005, at the age of 20, Keith was diagnosed with Facioscapulohumeral Dystrophy (FSHD). Three years later, in 2008, Keith and four friends cycled across Canada raising over $190,000 for Muscular Dystrophy Canada. Along the way, Keith inspired a nation to turn ideas into action.

"It's been a challenge overcoming the psychological effects of not having my body perform the way I feel it should. The sports I love have become harder and everyday tasks a little more difficult. I've gotten used to it, but I always notice it, and the adjustment is tough," says Keith about his diagnosis.

It's 2010 and Keith Martin's life is full. He graduated from the University of British Columbia in the spring, and is currently working in Montreal and looking forward to travelling the world.

FSHD is just one of more than 100 neuromuscular disorders. Each form is caused by an error in a specific gene related to muscle function. The symptoms of a neuromuscular disease vary according to the condition and may be mild, moderate or life-threatening. For some the disorder is fatal at a young age. No matter what the severity, entire families are affected. There is currently no cure. It is estimated that more than 50,000 Canadians are affected by a neuromuscular disorder.

Sensing a Breakthrough / Research News / News

2010-08-28T13:46:00.000-07:00

Sensing a Breakthrough
Aug 17 2010

When researchers pinpointed the genetic mutation that leads to the disease known as facioscapulohumeral dystrophy (FSHD) in 1992, hopes rose that the discovery not only would result in better treatments but also eventually a cure for the disease.

"It will take a worldwide effort to solve this disease and the Fields Center wants to be a big part of the effort," said van der Maarel. "I am always cautious about making predictions for the future so not to mislead patients. What we would consider major breakthroughs likely will take years before it makes a difference to the patient. But yes, we are close to breakthrough and I am looking forward to the coming years in the Fields Center."

Tapscott also avoids predictions, but like Tawil and van der Maarel, he is optimistic.

"I do not think about this in terms of a breakthrough but rather in terms of steady progress," Tapscott said.

(read entire article)

Media-Newswire.com - Press Release Distribution - PR Agency

2010-08-25T10:07:00.000-07:00

Nearly two decades after they identified the specific genetic flaw that causes a common type of muscular dystrophy, scientists believe they have figured out how that flaw brings about the disease.

The research was led by genetics researchers at the University of Leiden in the Netherlands, working together with scientists at the University of Rochester Medical Center, the Fred Hutchinson Cancer Research Center in Seattle, and other investigators. The research was funded by several organizations, including the Fields Center for FSHD and Neuromuscular Research, based at Rochester and at Leiden.

“It is amazing to realize that a long and frustrating journey of almost two decades now culminates in the identification of a single small DNA variant that differs between patients and people without the disease. We finally have a target that we can go after,” said Silvère van der Maarel, Ph.D., professor of medical epigenetics at Leiden and the corresponding author of the paper. Working closely with van der Maarel was the first author of the paper, Richard Lemmers of Leiden.

(read the complete article to learn more)

Zombie DNA linked to muscular dystrophy | The Cavalier Daily

2010-08-25T08:53:00.000-07:00

The Cavalier Daily

By Aradhya Nigam on August 25, 2010

Out of the entire human genome, only 2 percent is known to code for functional genes. The remaining 98 percent — known as “junk DNA.” — has generally been thought to be unused by the body. A study recently published in “Science,” however, has shown that certain sequences of junk DNA may have the ability to come back to life. This movie-like “Zombie DNA” has severe — and, perhaps, frightening — implications, as researchers have discovered a particular set of junk DNA that, once active, causes facioscapulohumeral muscular dystrophy, or FSHD, an inherited disease that causes weakening of the muscles of the face and shoulder. The study pinpointed a repeating set of “zombie DNA,” with a certain mutation causing it to become activated. Researchers are now looking for different treatments to avoid activating the set of DNA, thwarting cases of FSHD. Researchers are keen to continue “zombie” DNA research, as its success with explaining FSHD will hopefully help find treatments to other diseases as well.

—compiled by Aradhya Nigam

It is amazing that a form of muscular dystrophy rarely heard about & more rarely written about has been front page news around the world and on the net for the past week. Hopefully this notice will help us raise the monies needed to move this research to the much needed treatment. Friends of FSH Research is proud to have played a small role in this scientific breakthrough, funding Stephen Tapscott and other FSH scientists in the Seattle area since 2005.

FHCRC & UW Researchers Participate in Muscular Dystrophy Gene Discovery

2010-08-24T17:06:00.000-07:00

FHCRC & UW Researchers Participate in Muscular Dystrophy Gene Discovery

By Michael van Baker

Editor

Seattle/LocalHealthGuide has a story on the intercontinental team who have discovered the genetic link to a form of muscular dystrophy. Their paper, published in Science, details how expression of the DUX4 homeobox gene by an otherwise harmless stretch of "junk DNA" results in facioscapulohumeral muscular dystrophy (FSHD).

They're hypothesizing that the DUX4 protein is at some level toxic to muscle cell development, which results in FSHD's "weakness and wasting" of muscles in the face, shoulders, and upper arms--which can later reach the abdomen and hips. Eventually, it could be possible to medically disrupt the protein-encoding process--but for now identifying the protein in a lab's controlled conditions and in the body are two very different things.

(read more about the work at the Hutch and our researchers)

The curious genetics behind a form of muscular dystrophy | Seattle/LocalHealthGuide

2010-08-23T19:13:00.000-07:00

Dr Tapscott - Fred Hutchinson Research Center - A Friends of FSH Research Grant Recipient

A scientific team that included researchers from Europe, the University of Rochester and Seattle has worked out how a curious genetic mutation may cause a common form of muscular dystrophy.

People with the condition, called facioscapulohumeral muscular dystrophy or FSHD, develop muscle weakness starting in face, shoulders and upper arms.

The weakness tends to appear when a person reaches his or her teens, grows more severe with time and can eventually spread to other muscle groups. Severity can range from mild to disabling.

The findings of the new study may someday lead to a treatment for the disease.

Silvère M. van der Maarel, professor of medical epidgenetics at Leiden University Medical Center led the study in collaboration with Dr. Rabi Tawil, M.D. of the University of Rochester Medical Center and Dr. Stephen Tapscott of the Division of Human Biology at the Fred Hutchinson Cancer Research Center. Dr. Daniel Miller of the University of Washington was also on the research team.

The search for the gene

Dr. Stephen Tapscott

Early genetic studies indicated that the gene causing FSHD was located at the end of chromosome 4. But it was not clear exactly where the gene was.

One area of interest was a structure at the end of the chromosome called a macrosatellite repeat array. These arrays are composed of the same sequence of DNA repeated over and over again.

Such arrays occur commonly in our chromosomes, but are usually inactive.

(to learn more, read this article)

Cause of FSHD muscle disease discovered - News - News & Events

2010-08-23T17:13:00.000-07:00

FSHD Explained

Cause of FSHD muscle disease discovered

Researchers have known for some time that patients with the hereditary muscle disease FSHD lack part of chromosome 4. But there was uncertainty about how this leads to loss of muscle tissue. Researchers at the Leiden University Medical Center (LUMC) describe in an article in Science dated 19 August how the muscle damage comes about.

(here is a clear explanation for recent discoveries)

Research Moving Forward - Treatment Development Next

2010-08-23T17:09:00.000-07:00

Facioscapulohumeral dystrophy (FSHD) gene findings may help scientists find a cure for muscular dystrophy

Findings may help scientists find a cure for muscular dystrophy

After 20 years, researchers have discovered how a flawed gene can cause this incurable condition

By Tara Foss
WebMD Health News

Reviewed by Dr Rob Hicks

20^th August – Researchers from Europe and the US have found the specific DNA flaw in genes that causes people to have facioscapulohumeral dystrophy (FSHD). The defective gene produces a protein, called DUX4, that is toxic to muscles. It is this activity that is the key to whether people have FSHD or not.
The paper is published in the journal Science and is the result of a close collaboration between researchers from the Netherlands, France, Spain and the US.
"It is amazing to realise that a long and frustrating journey of almost two decades now culminates in the identification of a single small DNA variant that differs between patients and people without the disease. We finally have a target that we can go after," says Dr Silvère van der Maarel, one of the paper’s authors and professor of medical genetics at the University of Leiden in the Netherlands.

(read the whole article)

International Research Team Closes In On Cause of Common Form of Muscular Dystrophy - AlphaTrade Finance

2010-08-20T17:37:00.000-07:00

International Research Team Closes In On Cause of Common Form of Muscular Dystrophy

SEATTLE, Aug. 20 /PRNewswire/ -- An international team of researchers that includes investigators from Fred Hutchinson Cancer Research Center has made a critical advance in determining the cause of a common form of muscular dystrophy known as facioscapulohumeral dystrophy, or FSHD.

They have identified a DNA sequence in individuals with FSHD that causes a gene called DUX4 to be more active. Previous work from this research team and others has shown that this gene produces a protein that is toxic to muscle cells, and the current study indicates that it is likely to be key to developing FSHD. This finding points to potential new drug targets for treating - or potentially curing - FSHD, a progressive condition characterized by progressive wasting of muscles in the upper body.

The findings, published in the Aug. 20 issue of Science, shed new light on how a genetic mutation identified nearly 20 years ago causes the disease. The mutation is associated with the majority of FSHD cases, which affects some 300,000 people worldwide.

Researchers at the University of Leiden in the Netherlands led the study in collaboration with co-authors Stephen Tapscott, M.D., Ph.D., at the Hutchinson Center; Dan Miller, M.D., Ph.D., at the University of Washington; and Rabi Tawil, M.D., at the University of Rochester Medical Center, among others.

(read entire story at PRNewswire)

Scientists link a reawakened gene to muscular dystrophy - The Boston Globe

2010-08-20T08:49:00.000-07:00

Scientists link a reawakened gene to muscular dystrophy - The Boston Globe

By Gina Kolata
New York Times / August 20, 2010

NEW YORK — Identifying a new disease mechanism, geneticists have found that the reawakening of a gene in a stretch of seemingly useless, or junk, DNA causes a common form of muscular dystrophy.

It is almost certain, specialists say, that other diseases will be found to have similar causes. The discovery also points the way, they say, toward new research on treatment of this disease.

The human genome is riddled with so-called dead genes that have not been active for ages, part of a vast amount of the genome that has no known function. But this is the first time, geneticists say, that they have seen a dead gene come back to life and cause a disease.

The disease, facioscapulohumeral muscular dystrophy, or FSHD, was known to be inherited in a simple pattern. But before this research, reported online yesterday in Science by an international group of researchers, its cause was poorly understood.

The culprit gene is part of what has been called junk DNA, regions whose function, if any, is largely unknown. In this case, the gene had seemed permanently disabled.

FSHD affects about 1 in 20,000 people, causing a progressive weakening of muscles in the upper arms, around the shoulder blades, and in the face — people who have the disease cannot smile. It is a dominant genetic disease. If a parent has the gene mutation that causes it, each child has a 50 percent chance of getting it, too. And anyone who inherits the gene is certain to get the disease.

About two decades ago, geneticists zeroed in on the region of the genome that seemed to be the offender: the tip of the longer arm of chromosome 4, which was made up of a chain of repeated copies of a dead gene. The dead gene was also repeated on chromosome 10, but that area of repeats seemed innocuous, unrelated to the disease. Only chromosome 4 was a problem.

The more they looked at that region of chromosome 4, the more puzzling it was. No one whose dead gene was repeated more than 10 times ever got FSHD.

Researchers say those extra copies change the chromosome’s structure, shutting off the region.
© Copyright 2010 Globe Newspaper Company.

An International Collaboration Identifies a Region of DNA

2010-08-19T18:43:00.001-07:00

An international collaboration identifies a region of DNA necessary for FSHD and focuses attention on DUX4 as the cause of muscle deterioration

An international research collaboration that includes research groups funded by the Friends of FSH Research has made a critical advance in determining the cause of facioscapulohumeral dystrophy (FSHD). The mutation that causes the majority of FSHD cases was identified almost two decades ago but, in contrast to most genetic diseases, knowledge of the genetic mutation did not explain the cause of the disease. Although many different models and hypotheses were proposed for how the FSHD mutation might cause the disease, none had sufficient experimental support to attain legitimacy, which resulted in controversy and slow progress in FSHD research. The recent publication in Science magazine focuses research on a single and testable hypothesis. Their work identified a DNA variation (polymorphism) necessary for FSHD that occurs outside the mutation region and is necessary for FSHD. This DNA sequence in individuals susceptible to FSHD acts to stabilize the product of the DUX4 gene, whereas individuals not susceptible to FSHD have a different DNA sequence that does not stabilize DUX4. This finding provides a new and unifying model for FSHD because it focuses studies on determining whether the DUX4 protein causes FSHD, as indicated by this group’s genetic analysis.

This study, published in Science magazine, was led by Dr. Silvere van der Maarel at the Leiden University Medical Center, together with Dr. Rabi Tawil at the University of Rochester, Dr. Stephen Tapscott at the Fred Hutchinson Cancer Research Center in Seattle, and Dr. Dan Miller at the University of Washington in Seattle. Rapid progress was made possible by an unusual degree of collaboration and data-sharing among the individual groups at yearly workshops sponsored by the Friends of FSH research. The Friends of FSH Research, as well as the Shaw Family Foundation, sponsored yearly workshops that brought these collaborators together to share their research and also funded research in the laboratories of two of the groups (Dr. Stephen Tapscott at the Fred Hutchinson Research Center and Dr. Daniel Miller at the University of Washington). The initial progress supported by the Friends of FSH Research resulted in successful grant applications to the National Institutes of Health to continue their FSHD research studies.

Scientists Pinpoint Earliest Steps of Common Form of Muscular Dystrophy -- LEIDEN, The Netherlands, Aug. 19 /PRNewswire-USNewswire/ --

2010-08-19T17:54:00.000-07:00

Scientists Pinpoint Earliest Steps of Common Form of Muscular Dystrophy --
LEIDEN, The Netherlands, Aug. 19 /PRNewswire-USNewswire/ --

LEIDEN, The Netherlands, Aug. 19 /PRNewswire-USNewswire/ -- Nearly two decades after they identified the specific genetic flaw that causes a common type of muscular dystrophy, scientists believe they have figured out how that flaw brings about the disease. The finding by an international team of researchers settles a longstanding question about the roots of facioscapulohumeral muscular dystrophy or FSHD. The work is published in the August 20 issue of Science.

Read the complete article for more details.

Friends of FSH Research has been very pleased to have worked with S. Tapscott since 2006.

Junk DNA Can Revive and Cause Disease, Study Finds - NYTimes.com

2010-08-19T12:55:00.000-07:00

Junk DNA Can Revive and Cause Disease, Study Finds

The human genome is riddled with dead genes, fossils of a sort, dating back hundreds of thousands of years — the genome’s equivalent of an attic full of broken and useless junk.........

And the more they looked at that region of chromosome 4, the more puzzling it was. No one whose dead gene was repeated more than 10 times ever got FSHD. But only some people with fewer than 10 copies got the disease.

A group of researchers in the Netherlands and the United States had a meeting about five years ago to try to figure it out, and began collaborating. “We kept meeting here, year after year,” said Dr. Stephen J. Tapscott, a neurology professor at the University of Washington.

As they studied the repeated, but dead, gene, Dr. Tapscott and his colleagues realized that it was not completely inactive. It is always transcribed — copied by the cell as a first step to making a protein. But the transcriptions were faulty, disintegrating right away. They were missing a crucial section, called a poly (A) sequence, needed to stabilize them......

Thrilled to have the researcher we first funded in 2006 be recognized for this important work in a national publication - hopefully the awareness of FSHD and the importance of this research will be recognized.

FSHD Muscular Dystrophy Research Moving Forward

2010-08-19T11:27:00.000-07:00

International research team closes in on cause of common form of muscular dystrophy

SEATTLE – An international team of researchers that includes investigators from Fred Hutchinson Cancer Research Center has made a critical advance in determining the cause of a common form of muscular dystrophy known as facioscapulohumeral dystrophy, or FSHD.
They have identified a DNA sequence in individuals with FSHD that causes a gene called DUX4 to be more active. Previous work from this research team and others has shown that this gene produces a protein that is toxic to muscle cells, and the current study indicates that it is likely to be key to developing FSHD. This finding points to potential new drug targets for treating – or potentially curing – FSHD, a progressive condition characterized by progressive wasting of muscles in the upper body.
The findings, published in the Aug. 20 issue of Science, shed new light on how a genetic mutation identified nearly 20 years ago causes the disease. The mutation is associated with the majority of FSHD cases, which affects some 300,000 people worldwide.
Researchers at the University of Leiden in the Netherlands led the study in collaboration with co-authors Stephen Tapscott, M.D., Ph.D., at the Hutchinson Center; Dan Miller, M.D., Ph.D., at the University of Washington; and Rabi Tawil, M.D., at the University of Rochester Medical Center, among others.
"In contrast to most genetic diseases, knowledge of the genetic mutation did not explain the cause of the disease," said Tapscott, a member of the Human Biology Division at the Hutchinson Center and an expert in neurogenetics and neuromuscular disease. "Although many different models and hypotheses were proposed for how the FSHD mutation might cause the disease, none had sufficient experimental support to attain legitimacy, which resulted in controversy and slow progress in FSHD research. These new findings provide a single, testable hypothesis," Tapscott said.
The research group identified a DNA variation, or polymorphism, necessary for FSHD that occurs near the mutation region on chromosome 4 that was discovered nearly two decades ago. In those susceptible to this form of muscular dystrophy, this DNA mutation stabilizes the product of the DUX4 gene and thus causes the gene to be more active.
"This provides a new and unifying model for FSHD because it will focus future research on determining whether the DUX4 protein causes FSHD, as indicated by our consortium's genetic analysis," Tapscott said.
Corresponding author Silvere van der Maarel, Ph.D., professor of medical epigenetics in the Department of Human Genetics at Leiden University Medical Center in the Netherlands, led the study in collaboration with Tapscott and Tawil, who is a professor of neurology and director of the Fields Center for FSHD and Neuromuscular Research, which is based at the University of Rochester and at the University of Leiden.
These researchers have an ongoing collaboration through a Hutchinson Center-based National Institutes of Health FSHD Program Project Grant, of which Tapscott is principal investigator. This paper is the second to emerge from this collaboration.
"The progress was made possible by an unusual degree of collaboration and data-sharing among the individual groups," Tapscott said.

###

Grants from the Friends of FSH Research, the Shaw Family Foundation and the Muscular Dystrophy Foundation also supported the work of Tapscott and colleagues at the Hutchinson Center.

FSHD Research - Field's Center

2010-08-10T10:24:00.000-07:00

Sensing a Breakthrough - Rochester Medicine - Summer 2010 - University of Rochester Medical Center

Sensing a Breakthrough

Unique International Collaboration Advances Understanding and Treatment of a Muscular Dystrophy

By Michael Wentzel

Rabi Tawil, M.D.

When researchers pinpointed the genetic mutation that leads to the disease known as facioscapulohumeral dystrophy (FSHD) in 1992, hopes rose that the discovery not only would result in better treatments but also eventually a cure for the disease.
But FSHD, which was first described by French physicians in 1884, is an atypical genetic disease. While the discovery of the genetic defect on chromosome 4 opened new areas of research, it also added to the disease mysteries. This genetic defect involves the loss of a critical number of repetitive pieces of DNA, a sequence called D4Z4. At least 11 copies of the sequence are required for normal health. Those who have fewer than 11 get the disease.

Aerobic Exercise & Cognitive Therapy - FSHD

2010-08-08T10:20:00.000-07:00

Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial

Abstract

Background

In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated.

Myoblasts from affected and non-affected FSHD muscles

2010-08-07T13:53:00.000-07:00

Read complete manuscript @ https://mail.google.com/mail/?ui=2&view=bsp&ver=ohhl4rw8mbn4

Research study Manuscript for J Cell Mol Med
Marietta Barro 1 , Gilles Carnac 1 , Sébastien Flavier 1 , Jacques Mercier 1 2 , Yegor Vassetzky 3 , Dalila Laoudj-Chenivesse 1 *

Several papers support a role for oxidative stress as a pathological cause in FSHD [38 ,39 ]. Free radicals may be part of a cascade, and may provide a biochemical tool by which the pathological process can be inhibited. More studies on the action of radical oxygen species (ROS) and their sources may lead to a better understanding of the basis of FSHD. Indeed, the demonstration that alterations in specific oxidant species or in their cognate antioxidant systems are a triggering event that leads to abnormalities in FSHD satellite cells would then have pathological value and represent molecular targets for therapeutic and diagnostic development.

In conclusion, this study shows that myoblasts derived from both clinically unaffected and affected muscles of patients with FSHD are more susceptible to oxidative stress than control myoblasts. Moreover, although myoblasts from patients affected with FSHD fully differentiated into multinucleated myotubes, they fused to form either thin and branched myotubes with aligned nuclei or large myotubes with random nuclei distribution. These two phenotypes might be the consequence of differences in oxidative stress sensitivity. Alternatively additional signaling pathways may contribute either independently or cooperatively with oxidative stress in FSHD. It has been shown that overexpression of FRG1 in transgenic mice induces skeletal muscle atrophy [9 ]. By comparing genome-wide gene expression data from muscle biopsies of patients with FSHD to those of 11 other neuromuscular disorders, paired-like homeodomain transcription factor 1 (PITX1) was found specifically upregulated in patients with FSHD [14 ]. Since DUX4 protein can activate PITX 1 promoter, both DUX4 and PITX1 in FSHD muscles may play critical roles in the molecular mechanisms of the disease [14 ].

Therefore, these abnormalities could be responsible for the muscle weakness observed in patients with FSHD and provide an important marker for FSHD myoblasts.

Muscle Stem Cells - A Window into Cell Behavior

2010-08-06T18:20:00.000-07:00

Muscle Stem Cells as Seen on Time Lapse Photography

By Rob Granter | Saturday,August 7, 2010

When muscle tissue experiences trauma or disease, such as muscular dystrophy, stem cells in the muscle known as “satellite cells” respond to repair and regenerate the muscle.

(click link to read whole article & view the time lapse movie of these cells)

CoQ10

2010-08-05T19:54:00.000-07:00

Everything You Needed To Know About CoQ10

Some Information about CoQ10...
CoQ10 is a vitamin-like compound that is produced naturally in the human body and is also found in most living organisms. It is also called ubiquinone, a combination of quinone, a type of coenzyme, and ubiquitous, meaning it exists everywhere in the human body. CoQ10 plays an important role in your body’s energy production and is an essential component of the mitochondria, where it helps to metabolize fats and carbohydrates and maintain cell membrane flexibility. CoQ10 is also involved in the production of several key enzymes that are used to create ATP, which is burned by your body for energy, and in the energy transfer between mitochondria and cells. Without CoQ10, you would not be able to function!

More information is in this article, unfortunately no references are sited nor is there a name of the writer.
May present some data that should be verified.

Clinical profile and molecular diagnosis in patients of facioscapulohumeral dystrophy from Indian subcontinent Tamhankar PM, Phadke SR Neurol India

2010-07-28T13:03:00.000-07:00

Clinical profile and molecular diagnosis in patients of facioscapulohumeral dystrophy from Indian subcontinent
Tamhankar PM, Phadke SR Neurol India

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular dystrophy. We retrospectively studied three families (two Indian, one Nepalese) with 12 affected members (male:female-7:5). Mean age at onset of weakness was 17.63 + 5.48 years. Patients were classified according to muscle groups affected (F-face, S-scapula, H-humeral, PG-pelvic girdle, P-peroneal, A-loss of independent ambulation): FSH-A (2), four FSH (4), SH (3), FSH-PG (2) and one: F (1). Progression of weakness was classified as F>S>P>PG in eight cases, S> F>P in one, static in three. Eleven patients had electromyographic findings suggestive of myopathy and one had features of neurogenic involvement. Molecular diagnosis was done by southern blotting using probe p13E-11 after digestion of genomic DNA with EcoRI and/or EcoRI/BlnI for twelve patients and three unaffected relatives. No EcoRI fragment smaller than 35 Kb was seen in unaffected subjects. Size of EcoRI fragment varied between 17 kb to 27 kb in affected subjects and was constant for affected members of the same family. Molecular diagnosis by southern blotting has helped to provide genetic counseling for the families.

Myotonic Dystrophy & FSHD Registry - University of Rochester Medical Center

2010-07-16T16:56:00.000-07:00

Newsletters - Myotonic Dystrophy & FSHD Registry - University of Rochester Medical Center

Learn more about the Registry at the University of Rochester.

Read their past newsletters & see how you might get involved in a study and help advance FSH research.

Scientists develop new way to grow adult stem cells in culture

2010-07-15T18:49:00.000-07:00

Scientists develop new way to grow adult stem cells in culture

Scientists develop new way to grow adult stem cells in culture
July 15, 2010

Researchers at the Stanford University School of Medicine have developed a technique they believe will help scientists overcome a major hurdle to the use of adult stem cells for treating muscular dystrophy and other muscle-wasting disorders that accompany aging or disease: They've found that growing muscle stem cells on a specially developed synthetic matrix that mimics the elasticity of real muscle allows them to maintain their self-renewing properties.

Research connection - FSHD Global

2010-07-15T09:51:00.000-07:00

Research connection

Monash University
Research connection
July 2010

For Dr Lucy Burns, (MBBS 1993) supporting Monash research into Facioscapulohumeral muscular dystrophy (FSHD) is a cause close to her heart.

The President of the Victoria Branch of the FSHD Global Research Foundation and Monash medicine alumna is living with FSHD - the most common form of adult muscular dystrophy - and as an inherited disorder, there is a 50 per cent chance her children will grow up to develop the disease.

The foundation has donated $160,000 to Professor Christina Mitchell's team to analyse the levels and distribution of novel proteins that regulate muscle mass in human FSHD skeletal muscle samples, and to study muscle wasting in a mouse model of the disease.

Clinical trials

2010-07-13T10:43:00.000-07:00

Clinical trials | Muscular Dystrophy Campaign

FSHD Clinical Trials Currently seeking participants.

FSHD standards of care and clinical trial readiness

2010-07-13T10:08:00.000-07:00

FSHD is the third most common muscle disorder and although no definite cure exists, careful management of the symptoms can lead to significant improvements in quality of life. This workshop brought together patient representatives, clinicians and scientists to define standards of care and discuss what is needed to lay the foundation for future treatments. Recommendations were based on evidence, when available, or on the consensus of expert opinion.
Four main topics were discussed:

* Diagnosis
* Clinical management
* Clinical trial readiness
Future Plans

Read more at http://www.muscular-dystrophy.org/research/news/2481

Medical Marijuana: - FSH Pain Management

2010-07-03T13:39:00.000-07:00

Cañon City Daily Record - Medical Marijuana: Pro vs. Con

There are 21,625 registered medical marijuana patients in the state as of Oct. 31, 2009, according to the Colorado Department of Public Health and Environment, which is tasked by statute with issuing medical marijuana licenses.

Katy Klingbeil, 36, of Buena Vista, is one of those patients.

Klingbeil suffers from Facioscapulohumeral Muscular Dystrophy, FHS. The disease has caused her to lose muscle in her upper arms, shoulders, jaw and back.

Effect of aerobic exercise training

2010-07-02T10:29:00.000-07:00

Effect of aerobic exercise training and cognitive ... [BMC Neurol. 2010] - PubMed result

Abstract

ABSTRACT: BACKGROUND: In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain.

FSH presenting with hypertrophic cardiomyopathy: A case study

2010-06-28T13:35:00.000-07:00

Facioscapulohumeral muscular dystrophy presenting with hypertrophic cardiomyopathy: A case study: "Abstract

Only three facioscapulohumeral muscular dystrophy (FSHD) patients have been reported to have cardiomyopathy. An asymptomatic 38-year-old man was incidentally found to have electrocardiographic abnormalities. His echocardiogram demonstrated mild dilatation of the left ventricle and poor contractility. Cardiac histopathology indicated hypertrophic cardiomyopathy. Later he developed muscle weakness in the right arm. Scapular winging and asymmetrical facial weakness were evident. Muscle biopsy at the age of 44 years showed myopathic changes consistent with FSHD. His daughter had symptoms of infantile FSHD, which was genetically confirmed. This is the first report of an FSHD patient with biopsy-proven cardiomyopathy."

Gene Therapy Shows Promise

2010-06-19T08:52:00.000-07:00

Gene Therapy Shows Promise for Muscular Dystrophy | Science News

Scientists have succeeded in using gene therapy to restore some muscle function in patients with a certain type of muscular dystrophy.

“This study provides additional information regarding the feasibility of gene therapy for the treatment of muscular dystrophy,” said Dr. Valerie Cwik, executive vice president and research and medical director of the Muscular Dystrophy Association, which helped fund the research. “Specifically, it provides proof of principle, in people, for sustained gene expression [for at least six months] following treatment.”

This is the first time such a feat has been performed in humans, state the authors, who are presenting their findings at the annual meeting of the American Society of Gene & Cell Therapy in Washington, D.C.

(for more information, read the complete article)

genetic and epigenetic face of Facioscapulohumeral muscular dystrophy

2010-06-08T10:04:00.000-07:00

The genetic and epigenetic face of Facioscapulohumeral muscular dystrophy
Silvère van der Maarel, PhD, Prof.

Autosomal dominant Facioscapulohumeral Muscular Dystrophy (FSHD) is the second most common myopathy in adults. FSHD is mainly characterized by progressive and often asymmetric weakness and wasting of the facial, shoulder and upper arm muscles. During disease progression, also other muscles may become affected. Frequently reported non-muscular symptoms include sensorineural deafness and retinovasculopathy, although these symptoms often go unnoticed. Genetically, FSHD is associated with a contraction of the D4Z4 macrosatellite repeat in the chromosome 4q subtelomere in the large majority of patients. In healthy individuals this polymorphic repeat varies between 11-100 D4Z4 units, each unit being 3,3kb in size. Patients with FSHD typically carry one allele with a D4Z4 repeat of 1-10 units.

Click here to read more

Life Without a Smile

2010-05-29T11:02:00.000-07:00

MDA / Quest 4-3 / Life Without a Smile

COPING WITH FACIAL WEAKNESS IN FSHD

by Margaret Wahl

Songs tell us we're never fully dressed without a smile and exhort us to pack up our troubles in our old kit bags and -- smile, smile, smile. Smiling mouths tell us to buy everything from toothpaste and shampoo to diamonds and automobiles, and stylized "smiley faces" peer at us from posters and stickers.

There's more space in the brain devoted to muscle control of the face than to any other part of the body except the hands. And, a part of the brain known as the amygdala has as one of its specific functions the interpretation of other people's facial expressions.

Smiling is considered a milestone in a baby's life, one anxiously awaited by parents. ("Is it a smile, or is it just gas?" they wonder. "Is the baby connected to us yet?")

But, what about people, like many with facioscapulohumeral muscular dystrophy (FSHD), who can't smile? For many with this condition, weakness in the facial muscles makes any facial expression difficult, and smiling is particularly hard.

Paul Topkin of Lakeland, Fla., has his picture taken fairly often, mostly because of his recent fame as a builder of replicas of historic ships that sell for thousands of dollars to individuals and corporations.

Some people might see a photo of the 56-year-old Topkin and think he's a rather grim-looking artist, perhaps in need of treatment for depression. But Topkin has FSHD and, despite a lively sense of humor, he can't smile.

To Read More

DUX4c Is Up-Regulated in FSHD

2010-05-21T10:02:00.000-07:00

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. We have now characterized the homologous DUX4c gene mapped 42 kb centromeric of the D4Z4 repeat array. It encodes a 47-kDa protein with a double homeodomain identical to DUX4 but divergent in the carboxyl-terminal region. DUX4c was detected in primary myoblast extracts by Western blot with a specific antiserum, and was induced upon differentiation. The protein was increased about 2-fold in FSHD versus control myotubes but reached 2-10-fold induction in FSHD muscle biopsies. We have shown by Western blot and by a DNA-binding assay that DUX4c over-expression induced the MYF5 myogenic regulator and its DNA-binding activity. DUX4c might stabilize the MYF5 protein as we detected their interaction by co-immunoprecipitation. In keeping with the known role of Myf5 in myoblast accumulation during mouse muscle regeneration DUX4c over-expression activated proliferation of human primary myoblasts and inhibited their differentiation. Altogether, these results suggested that DUX4c could be involved in muscle regeneration and that changes in its expression could contribute to the FSHD pathology.

Read Complete research report

Toolbar for FSH Research

2010-05-17T19:20:00.000-07:00

Another way you can help MAKE A DIFFERENCE!

It's the new Pacific Northwest Friends of FSH Research toolbar - once added to IE or Firefox, each time you shop at more than 1,300 stores (from Amazon to Zazzle!) a percentage of your purchase will automatically be donated to Pacific Northwest Friends of FSH Research - at no cost to you (and you may even save money as the toolbar provides coupons and deals as well!).
The toolbar also has a search box and each time you search the Internet, about a penny is donated to Pacific Northwest Friends of FSH Research.

http://www.goodsearch.com/toolbar/pacific-northwest-friends-of-fsh-research

FSHD Review

2010-05-14T14:58:00.000-07:00

Natural History

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by progressive muscle weakness involving the face, scapular stabilizers, upper arm, lower leg (peroneal muscles), and hip girdle [Tawil et al 1998]. Asymmetry of limb and/or shoulder weakness is common [Kilmer et al 1995]. Typically, individuals with FSHD become symptomatic in their teens, but age of onset is variable. More than 90% of affected individuals demonstrate findings by age 20 years. Individuals with severe infantile FSHD have muscle weakness at birth. In contrast, some individuals remain asymptomatic throughout their lives. Progression is usually slow and continuous; however, many affected individuals describe a stuttering course with periods of disease inactivity followed by periods of rapid deterioration. Eventually 20% of affected individuals require a wheelchair.

To Read the complete report in Gene Link go to:

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=fsh

Neuromuscular Electrical Stimulation Training

2010-05-12T09:13:00.000-07:00

Physical Therapy Approach to FSHD

Arch Phys Med Rehabil. 2010 May;91(5):697-702.

Neuromuscular electrical stimulation training: a safe and effective treatment for facioscapulohumeral muscular dystrophy patients.

University of Nice-Sophia Antipolis, Laboratory of Human Motricity, Education, and Health, Faculty of Sports Sciences, Nice Cedex, France.

Abstract

OBJECTIVE: To investigate the feasibility, safety, and effectiveness of neuromuscular electrical stimulation (NMES) strength training in facioscapulohumeral muscular dystrophy (FSHD) patients.

DESIGN: Uncontrolled before-after trial.

SETTING: Neuromuscular disease center in a university hospital and a private-practice physical therapy office.

PARTICIPANTS: FSHD patients (N=9; 3 women, 6 men; age 55.2+/-10.4y) clinically characterized by shoulder girdle and quadriceps femoris muscle weakness.

INTERVENTIONS: Patients underwent 5 months of strength training with NMES bilaterally applied to the deltoideus, trapezius transversalis, vastus lateralis, and vastus medialis muscles for five 20-minute sessions per week.

MAIN OUTCOME MEASURES: Plasma creatine kinase (CK) activity; scores for pain and fatigue on visual analog scales (VAS), manual muscle testing (MMT), maximal voluntary isometric contraction (MVIC), 6-minute walking tests (6MWT), and self-reported changes in daily living activities.

RESULTS: NMES strength training was well tolerated (CK activity and pain and fatigue scores on VAS were not modified). Most of the muscle functions (shoulder flexion and extension and knee extension) assessed by MMT were significantly increased. MVIC of shoulder flexion and abduction and the 6MWT distance were also improved.

CONCLUSIONS: In FSHD, NMES strength training appears to be safe with positive effects on muscle function, strength, and capacity for daily activities.

MDA / Quest Extra / Abnormal Activation

2010-05-09T11:22:00.000-07:00

MDA / Quest Extra / Abnormal Activation

Abnormal Activation
New findings show abnormally activated parts of a gene called DUX4 may underlie FSH dystrophy

An MDA-supported team of scientists in the United States and the Netherlands has uncovered new leads about the origins of facioscapulohumeral muscular dystrophy (FSHD), a disease whose biochemical underpinnings have proved elusive to scientists despite years of investigation.

Lack of understanding of the mechanisms involved in FSHD has impeded treatment development, a phase of research that generally moves forward after disease mechanisms have been described.

About FSHD

FSHD is a form of muscular dystrophy that preferentially affects the muscles of the face ("facio"), shoulder ("scapulo") and upper arm ("humeral"). Affecting both males and females, it usually begins by age 20 and progresses slowly.

Difficulty smiling and upper-body weakness are typical of FSHD. The development of treatments has been hampered by lack of understanding of the disease process. This new research finding provides important clues to this process.

The genetic cause, a missing stretch of DNA (DNA "deletion") on chromosome 4, has been known since the 1990s. But attempts to pin down the specific effects of the DNA deletion, such as by finding specific genes in or near the region that have been altered by it, has led to more confusion than answers.

About the new findings

The new findings, published in the July issue of Human Molecular Genetics, focus on a gene known as DUX4, located near the end of chromosome 4 in the same region that harbors the FSHD-causing DNA deletion.

MDA supported work done by Sara Winokur at the University of California-Irvine, Silvere van der Maarel at Leiden University Medical Center in the Netherlands, and Galina Filippova at the Fred Hutchinson Cancer Research Center in Seattle. Rabi Tawil, who co-directs the MDA clinic at the University of Rochester (N.Y.) Medical Center, was also on the study team.

The researchers built on many previous studies, many of which have suggested that the loss of a DNA on chromosome 4 releases a molecular brake, activating genes in or near the deletion-containing region that would otherwise be inactive. Much of the focus until now has been on inappropriate activation of a chromosome-4 gene called FRG1.

DUX4 has been previously investigated as a culprit in FSHD, and some researchers found it to be active, whereas others have believed it to be inactive.

The new research supports both positions. DUX4 is for the most part inactive, it seems. However, it now appears that in FSHD-affected cells, pieces of DUX4 DNA are activated. They're transcribed into RNA (the first step a cell takes when making a protein molecule from an activated stretch of DNA) and some of these RNA pieces can then be translated into protein molecules.

One of the protein molecules made from the partially activated DUX4 gene was found to interfere with muscle development in cells in the laboratory. Other protein and RNA molecules from the abnormally activated DUX4 gene could have toxic effects as well, the researchers say. Therefore, any of them have the potential to become targets for therapeutic development.

Meaning for patients

There is no immediate potential for treatment from the new findings. However, if blocking or destroying one or more of the toxic pieces of RNA or protein improves or stabilizes weakness in an animal model of FSHD, a biotechnology company could become interested in developing the concept into a drug for human use. MDA supports this kind of drug development through its MDA Venture Philanthropy program (MVP).

If someone in your family has FSHD, you can help speed research by joining the National Registry of Myotonic Dystrophy & FSHD Patients and Family Members. This registry, supported by the National Institutes of Health and administered by the University of Rochester (N.Y.) Medical Center, connects patients with investigators.

'News from Friends of FSH Research'

2010-04-22T12:20:00.000-07:00

'News from Friends of FSH Research'
(Click link to view full newletter)

$6.3 Million Dollar Grant for FSH Research

Friends of FSH Research, based in Kirkland, WA. is thrilled to announce that a $6.3 million, 5-year National Institutes of Health (N.I.H.) grant for FSH research has been awarded to the Seattle-based research consortium headed by Dr. Stephen Tapscott. This is one of the largest grants ever to be awarded for Facioscapulohumeral Muscular Dystrophy research.

The grant from the Neurological Disorders and Stroke division of the N.I.H. will fund this 5-year research project entitled "The Pathogenesis of FSHD." This grant will support the work of several researchers, in various laboratories around the world. The overall project is under the administration of Dr. Tapscott at the Fred Hutchinson Research Center in Seattle, Washington.

The NIH project funding, which began on April 15, will support four different projects in the collaborating laboratories.

Project 1: The genetic and epigenetic basis for FSHD, Silvere van der Maarel, Leiden University Medical Center, Leiden, The Netherlands

Project 2: RNA regulation in FSHD, Stephen Tapscott, Fred Hutchinson Cancer Research Center, Seattle, WA

Project 3: The role of CTCF in chromatin and nuclear organization at the FSHD locus, Galina Filippova, Fred Hutchinson Cancer Research Center, Seattle, WA

Project 4: FSH patient derived IPS cells to study the developmental regulation of DUX4 transcription, Dan Miller, University of Washington, Seattle, WA

This collaborative project will work in partnership with Dr. Rabi Tawil at the Field's Center in Rochester, New York & utilize the resources of the Wellstone Center there.

Dr. Stephen Tapscott and Dr. Dan Miller were the second research team to receive funding from Friends of FSH Research for their pilot study "FSHMD Related Defects in Human Myogenesis" in 2006. They have continued to receive annual financial support from Friends of FSH Research over the past 4 years. We are extremely grateful to them for their dedication and we are delighted to have helped them earn this grant.

'News from Friends of FSH Research'

2010-04-22T11:59:00.000-07:00

'News from Friends of FSH Research'

Facioscapulohumeral Muscular Dystrophy [GeneReviews. 1993] - PubMed result

2010-04-21T14:40:00.000-07:00

Facioscapulohumeral Muscular Dystrophy [GeneReviews. 1993] - PubMed result:

"Facioscapulohumeral Muscular Dystrophy.

Lemmers RJLF, van der Maarel SM.
In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.
1999 Mar 08."

Excerpt

Disease characteristics. Facioscapulohumeral muscular dystrophy (FSHD) typically presents before age 20 years with weakness of the facial muscles and the stabilizers of the scapula or the dorsiflexors of the foot. Severity is highly variable. Weakness is slowly progressive and approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened. Diagnosis/testing. FSHD is diagnosed by a molecular genetic test that identifies deletion of integral copies of a 3.3-kb DNA repeat motif, D4Z4, which is located in the subtelomeric region of chromosome 4q35. Normal D4Z4 alleles have 11-100 repeat units; those associated with FSHD have between one and ten repeat units. Molecular genetic testing detects approximately 95% of affected individuals and is clinically available. Management. Treatment of manifestations: low-intensity aerobic exercise; ankle/foot orthoses to improve mobility and prevent falls; surgical fixation of the scapula to the chest wall may improve range of motion of the arms over the short term; standard treatment of sensorineural hearing loss; lubricants to prevent drying of the sclera or taping the eyes shut during sleep to treat exposure keratitis. Surveillance: annual evaluation to assess strength and functional limitations. Genetic counseling. FSHD is inherited in an autosomal dominant manner. Approximately 70%-90% of individuals have inherited the disease-causing deletion from a parent, and approximately 10%-30% of affected individuals have FSHD as the result of a de novo deletion. Offspring of an affected individual have a 50% chance of inheriting the deletion. Prenatal testing for pregnancies at increased risk is possible if the D4Z4 contraction mutation has been identified in the family.

(To read more, go to this link http://www.ncbi.nlm.nih.gov/pubmed/20301616)

Building muscle - Sharing the Work of Dr. Kyba

2010-04-17T12:47:00.000-07:00

Building muscle
Medical Bulletin Winter 2009
Minnesota Medical Foundation
University of Minnesota

Read about Dr. Michael Kyba - Friends of FSH Research's prior grant recipient

Searching for the best treatment target

To help steer future FSHD treatmentand cure-focused research down the right path, Kyba and his team are studying how the gene variation that causes FSHD, the third most common type of muscular dystrophy, causes muscle loss.

Scientists know that FSHD is caused by a missing piece of DNA that is part of a repetitive sequence. This area of DNA normally has about 100 copies of this particular sequence, Kyba says, but people who have FSHD have 10 or fewer copies.

“So there’s something in this repeat sequence that causes the disease when you have only 10 repeats but doesn’t cause the disease when you have more than 10 repeats,” he says. “Genetically, it’s a very mysterious disease.”

Kyba wants to know why this happens. By removing cells from people who have muscular dystrophy and reprogramming them to become induced pluripotent stem (iPS) cells, the team expects to gain insight into the genetic basis for this form of muscular dystrophy and hopes to find ways to genetically repair that diseasecausing defect.

“The protein encoded by this repetitive sequence is probably the best target for therapeutic intervention in FSHD, but we really haven’t proven it yet,” Kyba says. “We hope to use the iPS cells to show that the protein is expressed in muscle stem cells and validate that idea.”

Click above link to read entire article regarding University of Minnesota's Muscular Dystrophy works.

'News from Friends of FSH Research'

2010-04-12T08:51:00.000-07:00

'News from Friends of FSH Research'
April 2010

See about our recently awarded grant & other Friends of FSH Research News - just click the link to our newsletter!
Thanks

Collaborative Grant to University of Washington Researcher to Speed Therapy Development for FSH Dystrophy

2010-04-10T10:20:00.000-07:00

Collaborative Grant to University of Washington Researcher for Facioscapulohumeral Muscular Dystrophy

The Muscular Dystrophy Association (MDA), headquartered in Tucson, Ariz., and Friends of FSH Research (FFSHR), based in Kirkland, Wash., has jointly awarded a two-year, $200,000 grant to Dr. Joel Chamberlain, a research assistant professor of medical genetics at the University of Washington. The grant, equally funded by the two organizations, will enable the laboratory led by Dr. Chamberlain to study RNA interference as an investigative and therapeutic tool for facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy region gene-1 (FRG-1 is an actin-bundling protein associated with muscle-attachment sites.

2010-03-21T11:18:00.000-07:00

Facioscapulohumeral muscular dystrophy region gene-1
(FRG-1 is an actin-bundling protein associated with muscle-attachment sites.

Journal: J Cell Sci

Authors: Liu Q, Jones TI, Tang VW, Brieher WM, Jones PL

Published: 2010 Mar 9;

Pubmed ID: 20215405

In vertebrates, overexpression of facioscapulohumeral muscular dystrophy (FSHD region gene 1 (FRG1 recapitulates the pathophysiology exhibited by FSHD patients, although the role of FRG1 in FSHD remains controversial and no precise function for FRG1 has been described in any organism. To gain insight into the function and potential role of FRG1 in FSHD, we analyzed the highly conserved Caenorhabditis elegans ortholog, frg-1. C. elegans body-wall muscles contain two distinct subcellular pools of FRG-1: nuclear FRG-1, concentrated in the nucleoli; and cytoplasmic FRG-1, associated with the Z-disk and costamere-like structures known as dense bodies. Functionally, we demonstrate that FRG-1 is an F-actin-bundling protein, consistent with its localization to dense bodies; this activity is conserved in human FRG1. This is particularly intriguing because it places FRG-1 along side the list of dense-body components whose vertebrate orthologs are involved in the myriad myopathies associated with disrupted costameres and Z-disks. Interestingly, overexpressed FRG-1 preferentially accumulates in the nucleus and, when overexpressed specifically from the frg-1 promoter, disrupts the adult ventral muscle structure and organization. Together, these data further support a role for FRG1 overexpression in FSHD pathophysiology and reveal the previously unsuspected direct involvement of FRG-1 in muscle structure and integrity.

European Journal of Human Genetics - Abstract of article: Analysis of allele-specific RNA transcription in FSHD by RNA-DNA FISH in single myonuclei

2010-03-21T09:50:00.000-07:00

European Journal of Human Genetics - Abstract of article:
Analysis of allele-specific RNA transcription in FSHD by RNA-DNA FISH in single myonuclei

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is likely caused by epigenetic alterations in chromatin involving contraction of the D4Z4 repeat array near the telomere of chromosome 4q. The precise mechanism by which deletions of D4Z4 influence gene expression in FSHD is not yet resolved. Regulatory models include a cis effect on proximal gene transcription (position effect), DNA looping, non-coding RNA, nuclear localization and trans-effects. To directly test whether deletions of D4Z4 affect gene expression in cis, nascent RNA was examined in single myonuclei so that transcription from each allele could be measured independently. FSHD and control myotubes (differentiated myoblasts) were subjected to sequential RNA–DNA FISH. A total of 16 genes in the FSHD region (FRG2, TUBB4Q, FRG1, FAT1, F11, KLKB1, CYP4V2, TLR3, SORBS2, PDLIM3 (ALP), LRP2BP, ING2, SNX25, SLC25A4 (ANT1), HELT and IRF2) were examined for interallelic variation in RNA expression within individual myonuclei. Sequential DNA hybridization with a unique 4q35 chromosome probe was then applied to confirm the localization of nascent RNA to 4q. A D4Z4 probe, labeled with a third fluorochrome, distinguished between the deleted and normal allele in FSHD nuclei. Our data do not support an FSHD model in which contracted D4Z4 arrays induce altered transcription in cis from 4q35 genes, even for those genes (FRG1, FRG2 and SLC25A4 (ANT1)) for which such an effect has been proposed.

FSHD - Defined

2010-03-05T08:58:00.001-08:00

Awaiting the News - NIH Funding For FSHD Research in Seattle

2010-02-16T15:02:00.000-08:00

Dr. Stephen Tapscott, based at the Fred Hutchinson Research Center was one of the Friends of FSH Research's pilot grants in 2006. He and Dr. Dan Miller received a two-year grant for $100,000 for their study "FSHMD Related Defects in Human Myogenesis." This was just the beginning.....

A grant application was sent to NIH in May 2009 that includes several collaborative projects on FSHD to be conducted by the Fields Center in collaboration with the Fred Hutchinson Cancer Research Center in Seattle. This application will solidify the Fields Center’s collaboration with Dr. Stephen Tapscott’s laboratory in Seattle as well as bring in two additional research groups at the Fred Hutchinson Cancer Research Center solidly into the FSHD research arena. We are very hopeful that this proposal will be funded because of the strength of the research data presented and the fact that the Field Center provides the necessary infrastructure to assure the success of this venture. If funded, this project will significantly boost the research efforts into finding the cause of FSHD and the development of a rational approach to treatment.

from The Fields Center's, University of Rochester
Wellstone Muscular Dystrophy Center

We are eagerly and anxiously awaiting word from the NIH regarding this larger, more expansive grant application funding. If awarded, the Tapscott laboratories will have the funding to move this work at a more rapid pace and those with FSH Muscular Dystrophy will have reason to have great hope!

"FiSHing for a Cure" News and Updates

Need muscle for a tough spot?

Thanks for the Great Event - January 28th

Teams closing in on gene behind FSHD - FierceBiomarkers

Teams closing in on gene behind form of muscular dystrophy

DUX4 Causes Muscle Mayhem in FSHD

Kirkland Family Raises Funds for FSH Research

Kirkland Family Raises Funds for FSH Research

Joel Chamberlain RNAi Update

2010 Collaborative Grant - An Effective Means of Utilizing Limited Funds

Collaborative Grant to University of Washington Researcher toSpeed Therapy Development for FSH Dystrophy

Facioscapulohumeral muscular dystrophy: New diagnostic strategies

Friends of FSH Research Funded Project

Research team discovers genes and disease mechanisms behind a FSH muscular dystrophy

Discovery Could Lead to an Exercise Pill - Technology Review

DUX4 Activates Germline Genes - Research Supported by Friends of FSH Research

Advances in FSHD Research

Meeting with Bill Moss

Grants & Gala - Support FSH Research

FSHD Europe: The European voice of people with FSHD

PLOS Research Report - FSHD

Thank You for Being a Friend

Good Search for FSH Research

Whooping Cough - Risk to the Vulnerable

Collaborating Research Teams - Progress toward FSH Treatment

Two research teams make steps towards a treatment for FSH

Contents:

Background information

What did the research show?

What does this mean for FSH patients?

What about other conditions?

Big Stories - No Takers

FSHD and Standing Frame Exercise

Generosity of Strangers and Old Friends - Amazing Grace

Chris Carrino Foundation - The Power of One

The Ways to Cope With (FSHD) Facioscapulohumeral Muscular Dystrophy : Progressive Muscular Dystrophy

FSHD Foundation - Netherlands

NETS: Chris Carrino Foundation

Stem cell foundation for muscular dystrophy

Seeking Donations - Eager Recipient looking for Help!

FSHD - Overview

Facioscapulohumeral Muscular Dystrophy

GiveBig for FSHD research - June 23rd

Expression Profiling of FSHD-1 and FSHD-2 Cells during Myogenic Differentiation

Kirkland mother fights to fund research, find cure for son’s degenerative muscle disease

FSHD - 1st known human disease caused by unique circumstance

Facioscapulohumeral muscular dystrophy and DUX4: breaking the silence.

Abstract

NIH - Update FSH Research

Spotlight on Research 2011

Genetic Discovery Improves Understanding of FSH Muscular Dystrophy Cause

Major breakthrough in muscular dystrophy research

FSHD: copy number variations on the theme of muscular dystrophy — JCB

(click on title link to read entire report)

Conclusions

Ryan Levinson - Can’t choose what happens to you, only how you respond to it.”

New FSHD Findings - Summary

New research increases understanding of facioscapulohumeral muscular dystrophy.

Contents

What does the research show?

What does this mean for patients?

Inflammatory Role - Impacting FSHD Muscle Cells

CD8(+) T Cells in Facioscapulohumeral Muscular Dystrophy Patients with Inflammatory Features at Muscle MRI.

Abstract

Dave Matthews & Tim Reynolds - Singing for Charity

Accessibility on Melbourne's trams - Thanks Ray!

Friends of FSH Research - An international research consortium shows that FSHD muscle nuclei are poised for expression of the toxic DUX4 protein

FSHD: A Repeat Contraction Disease Finally Ready to Expand

Uncovering the Cause of a Common Form of Muscular Dystrophy: Research Team Makes Second Critical Advance | Science Magazine News

Uncovering the cause of a common form of muscular dystrophy

FSHD Muscular Dystrophy - Documentary

The challenge of unraveling the genetics of FSHD

Preliminary ACE-031 Results

A Unifying Genetic Model for FSHD - Review

Multi-National Research - Making Strides for FSHD Research

Running for FSHD Research

Runner - Andrew Prentice - Runs For FSH Research

New Report Regarding Fascioscapulohumeral Dystrophy

September is Muscular Dystrophy Awareness Month

Sensing a Breakthrough / Research News / News

Collaborative Grant to University of Washington Researcher to
Speed Therapy Development for FSH Dystrophy