The use of the exon skipping RNA editing method has shown preliminary success in treating a rare and severe form of muscular dystrophy that currently has no treatment, according to researchers at Northwestern Medicine and the University of Chicago. Their study (“Reengineering a transmembrane protein to treat muscular dystrophy using exon skipping”) is published in the Journal of Clinical Investigation.

The discovery stems from the persistence of Scott Frewing whose two sons were diagnosed with a rare and severe form of muscular dystrophy and his partnership with Elizabeth McNally, M.D., Ph.D. The rare form of the disease is Limb Girdle Muscular Dystrophy Type 2C.

Dr. 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. 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, Dr. McNally summarizes her research in fruit flies and mouse models. Her team, which included Quan Gao a University of Chicago graduate student and Eugene Wyatt, Ph.D., 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,” noted Dr. McNally. “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.

A new partnership among the University of Chicago, Northwestern University, and The Kurt+Peter Foundation will support the development of therapies for Limb Girdle Muscular Dystrophy Type 2C.

The McNally team is looking to clear the hurdles necessary to begin clinical trials. Obstacles remain to commercialize the treatment, including the high cost of manufacturing the antisense oligonucleotides, the molecules that function to regulate gene expression that are necessary to make the treatment.

“We are thrilled to be able to continue development of this promising treatment technique,” said Frewing, who is president of the Kurt+Peter Foundation. “This is a terrible disease affecting children worldwide, and we hope to soon be able to provide families with treatment techniques that can lessen the disease's severity.”

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