Research ArticleGene Therapy

Gene Therapy Prolongs Survival and Restores Function in Murine and Canine Models of Myotubular Myopathy

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Science Translational Medicine  22 Jan 2014:
Vol. 6, Issue 220, pp. 220ra10
DOI: 10.1126/scitranslmed.3007523

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Restoring Skeletal Muscle Function

X-linked myotubular myopathy is a fatal disease of skeletal muscle that affects about 1 in 50,000 male births. Patients harbor mutations in the MTM1 gene and are typically born floppy, with severely weak limb and respiratory muscles. Survival requires intensive support, often including tube feeding and mechanical ventilation, but effective therapy is not available for patients. Gene replacement therapy using adeno-associated viral (AAV) vectors has potential for the treatment of inherited diseases like myotubular myopathy. Therefore, Childers et al. tested the effects of a recombinant AAV vector expressing myotubularin in two animal models of myotubularin deficiency: Mtm1 knockout mice and dogs carrying a naturally occurring MTM1 gene mutation. Results in both mice and dogs showed that a single intravascular injection of AAV strengthened severely weak muscles, corrected muscle pathology, and prolonged survival. No toxicity or immune response was observed in dogs. These results demonstrate the efficacy of gene replacement therapy for myotubular myopathy in animal models and pave the way to a clinical trial in patients.