Medical Advances

Research Reveals Treatment for Rare Form of Muscular Dystrophy

rna technique for potential treatment rare limb-girdle muscular dystrophy type 2C

Main Article Content

RNA Technique May Delay Muscle Deterioration

When Scott Frewing started the Kurt + Peter Foundation in 2010 to fund research into the rare and severe form of muscular dystrophy affecting his two sons, there was one very clear choice for who should lead the work: Elizabeth McNally, MD, PhD, director of the Center for Genetic Medicine at Northwestern Medicine, one of the only genetic scientists studying the disease. The two formed a partnership that has since led to a breakthrough discovery on the path to treatment.

Limb-girdle muscular dystrophy type 2C (LGMD2C) is an inherited disorder that causes mutations in any of at least 15 different genes, most notably in a key protein that is necessary for muscle development and function. Very rare, it affects anywhere from 1 in 14,500 people to 1 in 123,000 people annually. Children can live normally at young ages, but deteriorating muscles eventually prevent their participation in everyday activities, and most are in a wheelchair by their mid-to-late teens.

When Frewing’s sons were diagnosed with LGMD2C, there was no treatment. But Frewing had heard of exon skipping, a technique originally developed for Duchenne muscular dystrophy, and approached Dr. McNally with the idea of adapting the treatment.

Enough to be Effective

Exon skipping is an RNA editing technique that causes cells to skip over abnormal sections of code so that the body can continue to make functional proteins, in this case for muscle development. Dr. McNally ran a predictive analysis applying exon skipping to LGMD2C and discovered that, while less than half of the necessary protein would remain, what was left included three key parts.

As the Elizabeth J. Ward Professor of Genetic Medicine, Dr. McNally has continued her research at Northwestern Medicine. A recent study summarizes her collective findings. Research with fruit flies and mouse models has shown that the protein made from exon skipping was functional and could stabilize and slow the progression of the disease, while work with human cells from individuals with the disease indicated that exon skipping could be successfully induced using antisense compounds, which act on the molecules involved in the creation of proteins.

The impact of this breakthrough could eventually be huge for those suffering from LGMD2C, perhaps allowing as many as 10 more years of walking and 20 to 30 more years of breathing. While this is only the first step, Dr. McNally and the Kurt + Peter Foundation hope to turn their findings into treatment and develop a therapy to slow the decline of muscle function.

Interested in hearing more from Northwestern Medicine? Sign up for the Healthy Tips E‑Newsletter for everything from health and wellness ideas to patient breakthroughs to academic and medical advancements.