| First Author | Childers MK | Year | 2014 |
| Journal | Sci Transl Med | Volume | 6 |
| Issue | 220 | Pages | 220ra10 |
| PubMed ID | 24452262 | Mgi Jnum | J:213528 |
| Mgi Id | MGI:5585235 | Doi | 10.1126/scitranslmed.3007523 |
| Citation | Childers MK, et al. (2014) Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy. Sci Transl Med 6(220):220ra10 |
| abstractText | Loss-of-function mutations in the myotubularin gene (MTM1) cause X-linked myotubular myopathy (XLMTM), a fatal, congenital pediatric disease that affects the entire skeletal musculature. Systemic administration of a single dose of a recombinant serotype 8 adeno-associated virus (AAV8) vector expressing murine myotubularin to Mtm1-deficient knockout mice at the onset or at late stages of the disease resulted in robust improvement in motor activity and contractile force, corrected muscle pathology, and prolonged survival throughout a 6-month study. Similarly, single-dose intravascular delivery of a canine AAV8-MTM1 vector in XLMTM dogs markedly improved severe muscle weakness and respiratory impairment, and prolonged life span to more than 1 year in the absence of toxicity or a humoral or cell-mediated immune response. These results demonstrate the therapeutic efficacy of AAV-mediated gene therapy for myotubular myopathy in small- and large-animal models, and provide proof of concept for future clinical trials in XLMTM patients. |
