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Long‐term effects of systemic gene therapy in a canine model of myotubular myopathy
Author(s) -
Elverman Matthew,
Goddard Melissa A.,
Mack David,
Snyder Jessica M.,
Lawlor Michael W.,
Meng Hui,
Beggs Alan H.,
BujBello Ana,
Poulard Karine,
Marsh Anthony P.,
Grange Robert W.,
Kelly Valerie E.,
Childers Martin K.
Publication year - 2017
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25658
Subject(s) - genetic enhancement , adeno associated virus , medicine , muscle weakness , transgene , myopathy , pathology , gene , vector (molecular biology) , biology , genetics , recombinant dna
X‐linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno‐associated virus (AAV) vector on muscle weakness and pathology in MTM1 ‐mutant dogs. Here, we followed 2 AAV‐infused dogs over 4 years. Methods We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression. Results Four years following AAV‐mediated gene therapy, gait, respiratory performance, neurological function and pathology in AAV‐infused XLMTM dogs remained comparable to their healthy littermate controls despite a decline in VCN and muscle strength. Conclusions AAV‐mediated gene transfer of MTM1 in young XLMTM dogs results in long‐term expression of myotubularin transgene with normal muscular performance and neurological function in the absence of muscle pathology. These findings support a clinical trial in patients. Muscle Nerve 56 : 943–953, 2017