There’s a rare disorder that occurs when a gene mutation halts the production of myotubularin—a protein that facilitates normal muscle function. The disease, called myotubular myopathy (MTM), only affects males, and it’s ultimately fatal because it causes breathing difficulties.
Dogs get MTM, too—and that spelled opportunity for scientists at the University of Washington Medicine Institute for Stem Cell and Regenerative Medicine. In collaboration with five other academic institutions, they found a way to replace the faulty MTM gene with a functioning gene in dogs with the disease, they reported in the journal Molecular Therapy.
It worked: After a single infusion of genes, muscle strength was restored in the dogs, according to a press release. One year later, the dogs were indistinguishable from healthy animals, they said. "This regenerative technology allowed dogs that otherwise would have perished to complete restoration of normal health," said Dr. Martin K. "Casey" Childers, UW Medicine researcher and physician.
The researchers used a viral vector called adeno-associated virus serotype 8 (rAAV8) to deliver a healthy canine version of the MTM gene in dogs that were 10 weeks old and already showing symptoms. They believe a similar trial could be designed in people.
Gene therapy is under investigation for a wide range of disorders, though much of the progress to date has occurred outside the realm of muscular disorders. BioMarin Pharmaceutical, for example, is in mid-stage trials of a gene therapy treatment for hemophilia A. UniQure is working on several gene therapy products to treat diseases including Huntington’s and congestive heart failure. Its most advanced project, a gene therapy product to treat hemophilia B, received breakthrough designation status from the FDA in January.
One company that has achieved some success with gene therapy in inherited muscle disorders is AveXis, which is gearing up for a pivotal trial of its treatment for spinal muscular atrophy. AveXis won breakthrough therapy designation for its gene product last year, and high hopes for the product have prompted its stock to more than triple since the company went public early last year.
UW Medicine-led team that worked on the canine MTM trial observed that as they increased the dosage of genes, survival rates improved, they reported. They believe the study proves the potential utility of gene therapy in a wide range of diseases that are linked to mutated genes.