Will Accelerate Discoveries in Myotonic Dystrophy and Related Genetic Diseases

The Myotonic Dystrophy Foundation (MDF) announced today that the U.S. House Appropriations Committee included a MDF led provision in the fiscal year 2023 Labor, Health and Human Services funding legislation (page 153) that will help establish a new Repeat Expansion Disease Initiative (REDI) at the National Institutes of Health (NIH) to increase federal funding for research on repeat expansions like myotonic dystrophy including new funding mechanisms across multiple institutes to support scientific discoveries that will lead to treatments and cures for myotonic dystrophy and related genetic disorders.

In related MDF research advocacy news, efforts continue to secure continued eligibility (sixth year in a row) for myotonic dystrophy research as part of the Department of Defense Peer-Reviewed Medical Research Program (PRMRP) and for a new myotonic dystrophy research funding line-item in the Congressionally Directed Medical Research Program (CDMRP). Advocacy continues as the Senate Appropriations committee considers their version of this legislation and a final bill that includes details on these programs are expected in the fall.

In the House report, the committee recognized the rapidly emerging science on DNA repeat expansions and cited myotonic dystrophy (DM1 and DM2) as being a paradigm for a class of diseases caused by repeat instability and toxic RNA. Based on the opportunity to advance new groundbreaking research, the Committee is asking NIH to establish a trans-NIH Repeat Expansion Disease Initiative (REDI) to increase federal funding for research on repeat expansions including new funding mechanisms across multiple institutes to support scientific discoveries that will lead to treatments and cures for myotonic dystrophy and related genetic conditions. Under the legislation, NIH is required to provide the committee with an update on these efforts in early 2023 as part of the President’s fiscal year 2024 budget justification.

Congressional report language provides more detailed guidance to departments and agencies than is provided in appropriations bills. The REDI provision reflects the final views of the House Appropriations committee and will take effect upon the start of the new fiscal year 2023 in October. MDF and our advocates are urging the Senate Appropriations committee to include identical language in their fiscal year 2023 report which is not yet finalized although companion Senate report language is not required for this initiative to move forward. MDF will be working with the NIH, Congress, and our research community help with the implementation of this exciting new research initiative. 

Repetitive sequences comprise most of the human genome and have been a major roadblock to obtaining the full sequence of the human genome. It was only recently that the NIH-funded T2T consortium was able to generate full, end-to-end sequencing of all human chromosomes, published in Science, in April 2022. These repetitive sequences are the source of over 50 (and growing) distinctive disorders caused by DNA repeat expansions. Myotonic dystrophy type 1 and 2 are repeat expansion diseases and have served as paradigms for a class of diseases caused by repeat instability and toxic RNA, which includes C9ORF72/amyotrophic lateral sclerosis/frontotemporal dementia, Huntington’s disease, and many common forms of dominantly inherited ataxia. Over the past several decades, researchers have begun to understand how these mutations drive pathogenesis in many of these diseases, but new repeat expansion diseases continue to be discovered, and the recent genome sequencing data described above provides a new roadmap for both normal and pathologic functions of repeats.

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by a CTG repeat expansion in the DMPK gene and a CCTG repeat expansion in the CNBP gene, respectively. These repeats are typically present in <30-50 contiguous copies in healthy individuals, but can expand to hundreds or thousands of copies in patients. These expansions prevent cells in the muscles, heart, and brain from functioning normally, leading to symptoms of myotonic dystrophy. Affecting as many as 1 in 2,100 individuals, myotonic dystrophy is the most common form of adult muscular dystrophy and considered the most variable of all known conditions; however, there is currently no cure and there are no approved treatments.

While U.S.-based researchers at the University of Florida, University of Rochester, Stanford University, Emory University, Baylor College of Medicine, and others are making progress to study how repeat expansions disrupt healthy gene regulation and cause disease symptoms, federal funding and coordination have been limited. Recognizing the current exciting landscape in biomedical research, the recently completed full sequence of the human genome, and emerging broad interest in repeat expansion diseases among patient advocacy groups and basic scientists, the Myotonic Dystrophy Foundation and our Scientific Advisory Committee urges Congress and the NIH to establish a new trans-NH Repeat Expansion Disease Initiative (REDI) within the Office of the NIH Director to fund new research and accelerate scientific discovery in this important new field. 

For example, we believe new federal research investments in the use of short- and long-read sequencing, high-throughput/high-resolution imaging, high throughput DNA synthesis technologies, and use of patient-derived cell biological tools/reagents will help scientists to better understand how the repeating RNAs cause a myriad of symptoms in virtually all tissues of the body, including skeletal, cardiac, and smooth muscle, and tissues of the central nervous system. We believe that new investments in studies of DM pathogenesis and RNA regulation will accelerate efforts to identify treatments and eventually cures for DM and other related diseases. 

The Myotonic Dystrophy Foundation (MDF) was founded in 2007 by families seeking answers and support. The MDF mission is "Community, Care and a Cure,": We support and connect the myotonic dystrophy community; We provide resources and advocate for care; We accelerate research toward treatments and a cure. Through direct services, research, education, and advocacy, MDF empowers the DM community, improves access to effective healthcare, and eliminates barriers to drug development. MDF is the leading global advocate helping individuals and families navigate the DM disease process and is often the first resource contacted by newly diagnosed patients, their families, their social workers, and their physicians around the world.

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