An RNA editing technique called “exon skipping” has shown preliminary success in treating a rare and severe form of muscular dystrophy that currently has no treatment, based on a new study from Northwestern Medicine and the University of Chicago. Children with the disease lose significant muscle strength early in life.
The discovery stems from the persistence of a father — Scott Frewing — whose two sons were diagnosed with a rare and severe form of muscular dystrophy and his search for and partnership with the genetic scientist — Dr. Elizabeth McNally — who studies the disease. The rare form of the disease is Limb Girdle Muscular Dystrophy Type 2C.
McNally is director of the Center for Genetic Medicine at Northwestern University Feinberg School of Medicine and the former director of the Institute of Cardiovascular Research at UChicago, which is where she began the research. She also is a physician at Northwestern Medicine.
The new therapy has been licensed to the Kurt+Peter Foundation, which supports Limb Girdle Muscular Dystrophy 2C research and is being developed with the goal of clinical trials and eventual commercial treatments. The boys’ family and friends started the foundation in 2010 to apply promising research to Limb Girdle Muscular Dystrophy Type 2C.
The finding will be published Oct. 12 in the Journal of Clinical Investigation.
Originally developed to treat Duchenne Muscular Dystrophy, another form of muscle disease, exon skipping coaxes cells to “skip” over abnormal sections of the genetic code, so that the body can make a functional protein, which in this case, governs muscle function and development.
In the paper, lead investigator McNally summarizes her research in fruit flies and mouse models. Her team, which included Quan Gao a University of Chicago graduate student and Dr. Eugene Wyatt, a postdoctoral fellow at Northwestern, demonstrated that protein made from exon skipping was functional to stabilize and slow progress of the disease. Working with human cells obtained from individuals with the disease, the team showed that exon skipping can be successfully induced with antisense compounds.
“We recognize that this is version 1.0,” McNally said. “But if this can stabilize individuals with this disease, even if it gave them 10 more years of walking, that’s huge. That would also mean 20 to 30 more years of breathing, and that is hugely beneficial for the patients and for their parents who are caring for them. And, of course, we’re interested in developing version 2.0 that will be even better.”
Limb Girdle Muscular Dystrophy is caused by mutations in any of at least 15 different genes and affects 1 in 14,500 to 1 in 123,000 annually. Individuals with Limb Girdle Muscular Dystrophy Type 2C have detrimental mutations in a key protein, gamma sarcoglycan, which is necessary for normal muscle development and function. The disease is an inherited disorder that is found in patients around the world and is prevalent in France, northern Africa and parts of South America.
Although children with the disease are able to live normally at young ages, over time their