Tuesday, June 30, 2009

Stem Cells - Research as Stanford University

Stem Cell News

A single cell can repopulate damaged skeletal muscle in mice, say scientists at the Stanford University School of Medicine, who devised a way to track the cell’s fate in living animals. The research is the first to confirm that so-called satellite cells encircling muscle fibers harbor an elusive muscle stem cell.

Identifying and isolating such a cell in humans would have profound therapeutic implications for disorders such as muscular dystrophy, injury and muscle wasting due to aging, disuse or disease.

“We were able to show at the single-cell level that these cells are true, multipotent stem cells,” said Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor of Pharmacology. “They fit the classic definition: they can both self-renew and give rise to specialized progeny.” Blau is the senior author of the research, which was published Sept. 17 in the online issue of Nature.

“We are thrilled with the results,” said Alessandra Sacco, PhD, senior research scientist in Blau’s laboratory and first author of the research. “It’s been known that these satellite cells are crucial for the regeneration of muscle tissue, but this is the first demonstration of self-renewal of a single cell.”

Stanford University

Monday, June 29, 2009

Fabulous Artist Support - Northwest Art Alliance

The ART 30 art fair, organized by the Northwest Art Alliance, was held at Magnuson Park in Seattle Washington on June 27th and 28th! Friends of FSH Research was welcomed as this year's community partner for this art show.

As the ART 30 partner, we were able to talk to the artists about our organization and our charity auction which will be held on January 30th. The generosity of the artists was amazing!!! We received many wonderful art pieces which will be sold at our auction to benefit FSHD research. Please check out our website (www.fshfriends.org) for the complete list of the donating artists.

Stem Cell Resources - Are they the Answer?

Stem Cell News -
Great Overview of Stem Cells.

".....with the dual ability to multiply indefinitely & differentiate into many tissue & cell types, embryonic stem cells hold vast potential for applications in regenerative medicine...."
"Latest Stem Cell News"

Stem Cell Surprise for Muscle Regeneration

article from the findings of the Carnegie Research Institution
From Medical News Today Website

Saturday, June 20, 2009

The Beginning of Something New in FSHD Research?

by Stephen Tapscott MD, PhD

Research on the cause and treatment of facioscapulohumeral muscular dystrophy (FSHD) might be entering a new, and hopefully better, era. For many years FSHD has been a difficult disease for medical researchers to study. In most genetic diseases, a gene with some known function is mutated and no longer performs its normal biological role. To find a treatment for such a disease, the medical researcher needs to identify therapeutic interventions that will compensate for the mutant gene. In contrast, FSHD removes a region of DNA with no known function, and, to make it yet more complicated, nearly identical copies of this region remain elsewhere in the genome. Although several researchers have proposed logical models of how the FSHD mutation might cause disease, there has not been strong experimental evidence to support any single model. This resulted in a lack of scientific consensus and, because scientific review committees rely on consensus, translated into difficulty competing for scarce research dollars.

Although it remains too early to claim that a new consensus is forming in the FSHD research community, there is now reason to hope that this is the case. Several publications have resurrected a hypothesis regarding the cause of FSHD that was originally suggested many years ago but largely abandoned because of the lack of experimental support. The hypothesis is that the region of DNA removed in the FSHD mutation has a normal role in suppressing gene expression from the remaining copies, and that expression of a gene in these copies called DUX4 might cause the disease. The problem with this hypothesis has been that researchers could not find any evidence that DUX4 was expressed in FSHD or in unaffected individuals.

Two recent publications now show expression of DUX4, or parts of DUX4, in FSHD and provide new support for this model of how the FSHD mutation causes muscle disease. Yi-Wen Chen at Children’s National Research Center in Washington, DC has reported evidence that DUX4 is expressed in FSHD muscle, and our group centered in Seattle has confirmed the expression of RNA from the DUX4 region and also showed that the RNA encoding the DUX4 protein is rapidly chopped-up, which might explain why it has been difficult to find in the past. Both our group and Michael Kyba at the University of Minneapolis have also shown that the DUX4 protein, or parts of the DUX4 protein that might be made from the chopped-up RNA, are toxic in muscle cells. Together, these studies provide experimental support for what has always been the most rational and attractive model of how the FSHD mutation causes a disease.

Our FSHD research group consists of my laboratory and several laboratories at the University of Washington and the Fred Hutchinson Cancer Research Center, as well as collaborators at the University of Rochester, the University of California Irvine, and Leiden Medical Center in The Netherlands. Support from the Friends of FSH Research made our work on this project possible.

If other groups can confirm our findings, and those of Kyba and Chen, then perhaps a new scientific consensus will develop in the research community. A generally accepted model for how the FSHD mutation causes disease will facilitate research proposals designed to find therapeutic interventions and will generate sufficient agreement in scientific review groups to make these proposals competitive for funding. This would certainly result in a new and better era for FSHD research, made possible, in part, by the support of the Friends of FSH Research.

Brian's Adventures In Korea

Brian Left for Korea 2 weeks ago - teaching English to a Middle School there.
To follow his adventures check out his website & blog at www.briancolella.com

Thursday, June 11, 2009

Athlete, Kristin Duquette

Introducing Kristin Duquette

Kristin is a student at East Catholic High School in Manchester, CT. She has been diagnosed with a form of muscular dystrophy (FSHD), but refuses to let this limit her ambitions in competitive swimming. Kristin is currently training for the Paralympic Games in London 2012.

Read more about Kristin on her own website

Go Kristin!

Thanks to Our Donors for Supporting This Research

RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: new candidates for the pathophysiology of FSHD

Deletion of a subset of the D4Z4 macrosatellite repeats in the subtelomeric region of chromosome 4q causes facioscapulohumeral muscular dystrophy (FSHD) when occurring on a specific haplotype of 4qter (4qA161).

Several genes have been examined as candidates for causing FSHD, including the DUX4 homeobox gene in the D4Z4 repeat, but none have been definitively shown to cause the disease, nor has the full extent of transcripts from the D4Z4 region been carefully characterized.
Using strand-specific RT–PCR, we have identified several sense and antisense transcripts originating from the 4q D4Z4 units in wild-type and FSHD muscle cells.
Consistent with prior reports, we find that the DUX4 transcript from the last (most telomeric) D4Z4 unit is polyadenylated and has two introns in its 3-prime untranslated region.
In addition, we show that this transcript generates

  • (i) small si/miRNA-sized fragments,
  • (ii) uncapped, polyadenylated 3-prime fragments that encode the conserved C-terminal portion of DUX4 and
  • (iii) capped and polyadenylated mRNAs that contain the double-homeobox domain of DUX4 but splice-out the C-terminal portion.

Transfection studies demonstrate that translation initiation at an internal methionine can produce the C-terminal polypeptide and developmental studies show that this peptide inhibits myogenesis at a step between MyoD transcription and the activation of MyoD target genes.
Together, we have identified new sense and anti-sense RNA transcripts, novel mRNAs and mi/siRNA-sized RNA fragments generated from the D4Z4 units that are new candidates for the pathophysiology of FSHD.

Human Molecular Genetics 2009 18(13):2414-2430
Lauren Snider1,{dagger}, Amy Asawachaicharn1,{dagger}, Ashlee E. Tyler1, Linda N. Geng1, Lisa M. Petek2, Lisa Maves1, Daniel G. Miller2, Richard J.L.F. Lemmers4, Sara T. Winokur5, Rabi Tawil6, Silvère M. van der Maarel4, Galina N. Filippova1 and Stephen J. Tapscott1,3,*

1 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA 2 Department of Pediatrics 3 Department of Neurology, University of Washington, Seattle, WA 98195, USA 4 Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands 5 Department of Biological Chemistry, University of California, Irvine, CA 92697, USA 6 Department of Neurology, University of Rochester, Rochester, NY 14642, USA

* To whom correspondence should be addressed at: Fred Hutchinson Cancer Research Center, Mailstop C3-168, 1100 Fairview Ave North, Seattle, WA 98109, USA. Tel: +1 2066674499; Fax: +1 2066676524; Email: stapscot@fhcrc.org Received January 5, 2009; Revised March 12, 2009; Accepted April 6, 2009

Wednesday, June 10, 2009

French FSHD Resource - AMIS FSH Europe

This site includes a great deal of practical information on FSHmuscular dystrophy and aims to communicate on this illness. It isintended for people or relatives affected by this disease.

The main goal of this site is to:

* Break through the isolation of families coping with the disease
* Encourage information exchanges on experiences of those affected by this disease
* Share information on FSH
* Support research on FSH

This is a great site to find news about FSHD research - another great source of information for those living with FSHD and their families.

Monday, June 8, 2009

Stem Cells Offer Hope

Stem cells offer hope for
muscle repair

Scientists hail discovery of protein that could lead to new treatments for debilitating diseases

Ottawa scientists have discovered a way to boost the body's ability to repair muscle tissue, a finding that could lead to new treatments for debilitating muscular diseases.

Read complete report from TheStar.com - News from Ottawa.

Saturday, June 6, 2009

Long Island FSHD Foundation

I am so pleased to announce the formation of another FSHD organization that is dedicated to promoting FSHD research!!
The Long Island FSHD Foundation, under the direction of Jennifer Valentine began this year and will hold their very first fundraising event on October 21, 2009. I wish them the best of luck & hope we will be able to work together in the future!!!


To learn more about this new organization visit their website at www.LIFSHD.com

Thursday, June 4, 2009

Patenting Human Genes Thwarts Research

I found this article to be very disturbing in that the research being supported is leading to genes being patented - the goal being personal glory & financial gain rather than the ultimate aim of improving the human condition.

The article published today in the Kansas City on-line news, states that more than 20% of the human genes have been patented which is a concern for those doing medical research.

"Twenty percent of the human genes are currently patented," said Christopher Hansen, an attorney for the American Civil Liberties Union, which filed a suit last month challenging six patents on two genes that are connected to tests for breast and ovarian cancer.

A gene patent gives its owner the exclusive right, for up to 20 years, to control its use for medical research, diagnosis or treatment."

The article goes on to say that there are numerous patents being filed creating a backlog and the effect of patenting genes has had detrimental effects.

"Fiona Murray, a professor of management at the Massachusetts Institute of Technology in Cambridge, reported a "significant decrease in the rate of follow-on research after patents on gene sequences have been filed and granted."

The Patent Office estimated that about 52,800 patents have been granted related to genes, fragments of genes, genetic processes and bits of DNA as small as a single letter change in the genetic code."

"It is curious--curious that physical courage should be so common in
the world, and moral courage so rare."

-Mark Twain

Tuesday, June 2, 2009

".....all the good that a simple smile can do"

Living with Muscular Dystrophy

Sarabjit Parmar describes living with muscular dystrophy and how she can do anything she wants, except smileFrom the day I was born I have never smiled.As a child I don't think I ever questioned it.

It sounds bizarre, but I never acknowledged that it was a physical impossibility.
The first time the seriousness of it really hit me was when I was in my teens....
Read the complete text at Guardian.co.uk

NIH Initiative for Rare & Neglected Diseases

NIH Announces New Program to Develop Therapeutics for Rare and Neglected Diseases

The National Institutes of Health (NIH) is launching the first integrated drug development pipeline to produce new treatments for rare and neglected diseases. The $24 million initiative jumpstarts the trans-NIH Therapeutics for Rare and Neglected Diseases (TRND) program.

The program is unusual because TRND creates a drug development pipeline within the NIH and is specifically intended to stimulate research collaborations with academic scientists working on rare illnesses. The NIH Office of Rare Diseases Research (ORDR) will oversee the program, and TRND’s laboratory operations will be administered by the National Human Genome Research Institute. Other NIH components will also participate in the initiative.

A rare disease is one that affects fewer than 200,000 Americans. NIH estimates that, in total, more than 6,800 rare diseases afflict more than 25 million Americans. However, effective pharmacologic treatments exist for only about 200 of these illnesses. Many neglected diseases also lack treatments. Unlike rare diseases, however, neglected diseases may be quite common in some parts of the world, especially in developing countries where people cannot afford expensive treatments. Private companies seldom pursue new therapies for these types of illnesses because of high costs and failure rates, and the low likelihood of recovering investments or making a profit.

"This initiative is really good news for patients with rare or neglected diseases," said ORDR Director Stephen C. Groft, PharmD. "While Congress has previously taken important steps to help these patients, such as providing incentives for drug companies under the Orphan Drug Act, this is the first time NIH is providing support for specific, preclinical research and product development known to be major barriers preventing potential therapies from entering into clinical trials for rare or neglected disorders. While we do not underestimate the difficulty of developing treatments for people with these illnesses, this program provides new hope to many people worldwide."

TRND will work closely with disease-specific experts on selected projects, leveraging both the in-house scientific capabilities needed to carry out much of the preclinical development work, and contracting out other parts, as scientific opportunities dictate. Its strategies will be similar to approaches taken by pharmaceutical and biotechnology companies, but TRND will be working on diseases mostly ignored by the private companies. Importantly, TRND will also devote some of its efforts to improving the drug development process itself, creating new approaches to make it faster and less expensive.

If a compound survives the preclinical stage, TRND will work to find a company willing to test the therapy in patients. There are several stages to the clinical trials process that can take several years before the safety and efficacy of a new drug is determined. The Food and Drug Administration will only approve a drug for general use after it passes these trials. The clinical trials process is also expensive, but the failure rate is lower at this stage. TRND will seek to take advantage of several NIH resources that can help launch human studies, including the NIH Clinical Center, the NIH Rapid Access to Interventional Development, and the Clinical and Translational Science Awards program.

Numerous obstacles impede the development of new drugs for rare and neglected diseases. In addition to the reluctance of private companies to risk their capital on a potentially low return, relatively few basic researchers study rare diseases, so the underlying cause of the illness frequently remains unknown. Also, because rare diseases are rare, researchers often have difficulty recruiting enough people with the disorder to participate in a clinical trial once a candidate compound reaches the stage where it can be tested in people. Moreover, for many rare diseases, the natural history of the disease is poorly understood, so researchers lack the needed clinical measures (such as blood pressure) that can demonstrate whether a treatment is working.

To address these difficulties, TRND will seek a wide range of collaborations with academic researchers, as well as partnerships with patient advocacy organizations, disease-oriented foundations, and others interested in treatments for particular illnesses. TRND’s leaders hope that the collaborations will help lay the groundwork for clinical trials once that point in drug development is reached.

TRND is currently setting up an oversight process to help it decide which projects that address thousands of rare and neglected diseases will be pursued. Leadership currently envisions a small number of diseases being studied each year, with strict criteria used to determine which molecules will be studied for which diseases. NIH expects to use existing intellectual property policies to transfer licenses for TRND-discovered drugs to private companies or others for development, clinical testing, and marketing.

Source: NIH News 5/20/09