Saturday, August 28, 2010

Sensing a Breakthrough / Research News / News

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)

Wednesday, August 25, 2010

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

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


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.

Tuesday, August 24, 2010

FHCRC & UW Researchers Participate in Muscular Dystrophy Gene Discovery

FHCRC & UW Researchers Participate in Muscular Dystrophy Gene Discovery

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)

Monday, August 23, 2010

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

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 in his lab

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

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

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
20th 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)

Friday, August 20, 2010

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

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

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.

Thursday, August 19, 2010

An International Collaboration Identifies a Region of DNA


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/ --

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

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

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

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.

Tuesday, August 10, 2010

FSHD Research - Field's Center

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.
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.

Sunday, August 8, 2010

Aerobic Exercise & Cognitive Therapy - FSHD


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.


Saturday, August 7, 2010

Myoblasts from affected and non-affected FSHD muscles

 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.

Friday, August 6, 2010

Muscle Stem Cells - A Window into Cell Behavior





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)

Thursday, August 5, 2010

CoQ10

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.