Type of Submission
Poster
Keywords
Gene Therapy, Duchenne Muscular Dystrophy, Genetic mutation
Proposal
Duchenne muscular dystrophy (DMD) is a universally fatal disease caused by a mutation in the DMD gene on the X chromosome. This mutation leads to a missing dystrophin protein—necessary for proper muscle function—in all striated muscle. DMD is characterized by progressive muscle weakness, loss of ambulation, and premature death. There is no cure, and the current standard of care combines corticosteroids, physical and occupational therapy, and corrective surgeries. Advanced cardiorespiratory life support is needed to prolong life. New gene therapies attempt to correct the root issue. Two of these therapies are exon-skipping and microdystrophin. Exon-skipping blocks the mutated portion of the DMD gene allowing the body to turn the remaining gene into a semi-functional protein. Microdystrophin uses a single injection of a virus to supply an abbreviated gene to all cells in the patient’s body leading to a functional protein. The purpose of this review is to determine if gene therapy is a viable treatment option to improve quality of life for boys with DMD.
Exon-skipping was the first gene therapy to be developed for DMD. A systematic review of exon-skipping therapies found two studies and three ongoing trials with at least 50 participants (aged 6–15 years). Reviewers observed an average dystrophin increase of 27% but had insufficient data to determine the change in quality of life for boys receiving these treatments.
In two studies on the second therapy, microdystrophin, treatment was provided using the medication Elevidys. The first study included four boys and the second 41 boys (all aged 4–8 years). The first study was open-label and non-random; the second was a two-part, double-blind, crossover study. Researchers used an external control group for both studies and evaluated functional outcomes using the North Star Ambulatory Assessment and safety outcomes using treatment-related adverse events. Both studies found significant improvement in all participants for all functional outcomes, and adverse events were mild or moderate. In conclusion, data was insufficient to support improvement with exon-skipping therapy but demonstrated that microdystrophin therapy greatly improved the quality of life for boys with DMD over the standard of care alone.
Copyright
© 2025 Tommy Squier. All rights reserved.
Publication Date
4-3-2025
Is gene therapy is a viable treatment option to improve quality of life for boys with Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a universally fatal disease caused by a mutation in the DMD gene on the X chromosome. This mutation leads to a missing dystrophin protein—necessary for proper muscle function—in all striated muscle. DMD is characterized by progressive muscle weakness, loss of ambulation, and premature death. There is no cure, and the current standard of care combines corticosteroids, physical and occupational therapy, and corrective surgeries. Advanced cardiorespiratory life support is needed to prolong life. New gene therapies attempt to correct the root issue. Two of these therapies are exon-skipping and microdystrophin. Exon-skipping blocks the mutated portion of the DMD gene allowing the body to turn the remaining gene into a semi-functional protein. Microdystrophin uses a single injection of a virus to supply an abbreviated gene to all cells in the patient’s body leading to a functional protein. The purpose of this review is to determine if gene therapy is a viable treatment option to improve quality of life for boys with DMD.
Exon-skipping was the first gene therapy to be developed for DMD. A systematic review of exon-skipping therapies found two studies and three ongoing trials with at least 50 participants (aged 6–15 years). Reviewers observed an average dystrophin increase of 27% but had insufficient data to determine the change in quality of life for boys receiving these treatments.
In two studies on the second therapy, microdystrophin, treatment was provided using the medication Elevidys. The first study included four boys and the second 41 boys (all aged 4–8 years). The first study was open-label and non-random; the second was a two-part, double-blind, crossover study. Researchers used an external control group for both studies and evaluated functional outcomes using the North Star Ambulatory Assessment and safety outcomes using treatment-related adverse events. Both studies found significant improvement in all participants for all functional outcomes, and adverse events were mild or moderate. In conclusion, data was insufficient to support improvement with exon-skipping therapy but demonstrated that microdystrophin therapy greatly improved the quality of life for boys with DMD over the standard of care alone.
