New research has shown that a RNA technique called “exon skipping” can successfully generate stable proteins and slow down a severe disease form of muscular dystrophy, Limb Girdle Muscular Dystrophy Type 2C. The research paper, entitled “Reengineering a transmembrane protein to treat muscular dystrophy using exon skipping”, was published in The Journal of Clinical Investigation.
The research, led by Dr. Elizabeth McNally, director of the Center for Genetic Medicine at Northwestern University Feinberg School of Medicine, showed that exon skipping, previously used to treat Duchenne Muscular Dystrophy, was also able to produce a stable protein that proved to be beneficial both functionally and pathological in severe Limb Girdle Muscular Dystrophy Type 2C, where an essential protein γ-sarcoglycan is mutated.
Exon skipping uses antisense oligonucleotides designed to skip premature stop codons in the coding sequence of RNA. The researchers used two models, Drosophila (fruit fly) and transgenic mice, observing the new protein, generated by exon skipping, stabilized and slowed down disease. Furthermore, the study also included a human disease cellular model, where scientists were able to generate multiple exon skippings in the RNA encoding the mutant form of γ-sarcoglycan, crucial for muscle development and function. Study author Dr. McNally commented on these results, “We recognize that this is version 1.0. 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.”
The new treatment approach has been licensed to The Kurt+Peter Foundation, founded by Scott Frewing and his family and friends, when his two sons were diagnosed with Limb Girdle Muscular Dystrophy Type 2C. In 2010, Frewing began looking for scientists who were studying the condition, eventually partening with Dr. McNally, one of the only scientists conducting research on the disease. Frewing’s persistence convinced the team to pursue research applying this RNA technique to his sons’ condition. The therapy is continuing to be developed and researchers are now prioritizing the beginning of clinical trials. Research will now be made in collaboration with the Kurt&Peter Foundation, University of Chicago and Northwestern.