Supporting research into Facioscapulohumeral Muscular Dystrophy.
Monday, November 12, 2012
Thursday, July 26, 2012
Platform development for candidate drug screening for FSHD
The Miller Lab has made exciting progress in the development of a platform for screening genes and compounds with activities that affect FSHD-specific pathogenic processes. This platform (developed using funds provided by The Friends of FSH Research and largely orchestrated by FSHD-Research Scholar Dr. Gregory Block) allows muscle cells to be cultured for long periods of time. Most cells when cultured outside of the body have a limited number of cell divisions before they simply stop dividing, however when expression of the CDK4 and Telomerase genes are “forced” in these cells, they continue to divide as if they had just been removed from someone’s muscle, a finding initially published by FSHD-researcher Dr. Gillian Butler-Browne. The improved longevity allows for careful study of a number of different characteristics in the same cells, and removes some of the experimental variability that is seen when comparing cells that have been allowed to divide for different lengths of time. Most significantly, we have optimized conditions that reveal FSHD-specific differences when cells from FSHD-affected individuals are compared to un-affected control individuals. While this may seem obvious, FSHD researchers have been plagued by the somewhat normal growth, differentiation, and lifespan of FSHD muscle cells, and the lack of physical differences in these cells when their growth characteristics are compared to cells derived from biopsies of normal muscles. Putting these two findings together will allow us to begin to efficiently search for genes and molecules that specifically prevent FSHD-cells from becoming sick. We are excited about the prospects for identification of drug targets that may be useful for developing treatments that slow or eliminate the muscle loss in FSHD.
Wednesday, July 25, 2012
Monday, April 16, 2012
New "DNA Combing" Test for FSHD
"Current diagnostic methods are laborious and provide results that are difficult to interpret," says Dr. Pierre Walrafen, project manager at Genomic Vision.
The methods Dr. Walrafen refers to are less accurate owing to the complications inherent in the causes of FSHD, and the new test will hopefully improve accuracy and effectiveness in testing for FSHD.
The Timone hospital in Marseille, France, has adopted the technology for regular use--an estimated 300 to 500 patients per year. Prof. Clemens Muller-Reible at the human genetics institute in the Biology Center of the University of Wurzburg is also deploying the method as a beta test.
Friday, February 3, 2012
Core Muscle Exercise For Muscular Dystrophy | LIVESTRONG.COM
Read more: http://www.livestrong.com/article/554471-core-muscle-exercise-for-muscular-dystrophy/#ixzz1lN7hf7kM
Thursday, February 2, 2012
Dr. Stephen Tapscott - Podcast on the MDA's Quest
Here is a link to a podcast which you might find interesting.
Dr. Tapscott presents his latest information about DUX 4 and thoughts regarding the future possibilities for FSH therapy.
Monday, January 30, 2012
Need muscle for a tough spot?
Thanks for the Great Event - January 28th
You, the many friends of FSH research, raised $161,500 on January 28th!
for spinning the tunes of the '60s & '70s
Sunday, January 22, 2012
Teams closing in on gene behind FSHD - FierceBiomarkers
Teams closing in on gene behind form of muscular dystrophy
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
Saturday, January 21, 2012
DUX4 Causes Muscle Mayhem in FSHD
- 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.
Wednesday, January 18, 2012
Kirkland Family Raises Funds for FSH Research
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.
Tuesday, January 17, 2012
2010 Collaborative Grant - An Effective Means of Utilizing Limited Funds
Collaborative Grant to University of Washington Researcher to
Monday, January 16, 2012
Facioscapulohumeral muscular dystrophy: New diagnostic strategies
Sunday, January 15, 2012
Friends of FSH Research Funded Project
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
Thursday, January 12, 2012
Research team discovers genes and disease mechanisms behind a FSH muscular dystrophy
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.
Wednesday, January 11, 2012
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.
Sunday, January 1, 2012
DUX4 Activates Germline Genes - Research Supported by Friends of FSH Research
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.