What is the role of gene therapy in the management of muscular dystrophy?

Updated: Aug 17, 2020
  • Author: Twee T Do, MD; Chief Editor: Jeffrey D Thomson, MD  more...
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Another novel method of treatment under intense investigation is somatic gene therapy, wherein healthy immature myoblasts are introduced into the diseased muscles, which then fuse and stimulate production of enough dystrophin to reverse the degeneration that occurs in the affected muscles. [49]

However, although somatic gene therapy has been achieved successfully in the X-linked muscular dystrophic mouse (murine MDX) model with the fusion of the donor and host muscle cells, which expressed some dystrophin, the benefit may not translate into human males. [49]  The mice cannot demonstrate muscle strength, and the laboratory-raised mice were not able to mount a rejection response that may occur in humans. Other investigations have been conducted on the canine MDX model, which more closely approximates the human condition. [50, 51]

Human trials of gene therapy began in 1990, with an uncontrolled trial of eight patients who were injected with myoblasts from family donors. [52]  Strength testing and staining for dystrophin was performed after several months. Early results demonstrated no improvement in patients' muscle strength or dystrophin staining. Later studies showed an increase in the expression of dystrophin proteins. However, the clinical results remain unchanged. These preliminary results, although disappointing, do not dampen the promise of gene therapy. Most supporters believe that these failures were merely the result of a lack of expertise, as with once-novel techniques such as organ transplantation.

Other molecular approaches to therapy include recombinant versions of the dystrophin gene using viral or nonviral vectors and antisense oligonucleotides. [53, 54]  In the viral vector therapeutic approach, adenosine-associated virus leads the way. [55]  In nonviral gene therapy, plasmid-mediated gene delivery, antisense-mediated exon skipping, and oligonucleotide-mediated gene editing has moved from successful trials in the lab to the clinic. In approximately 10-20% of the preclinical cases, [54]  it is possible to chemically persuade the translational machinery to read through a premature stop codon, as noted with the dystrophin mutation, and lead to production of a more functional full-length protein.

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