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Article Dans Une Revue Muscle & Nerve Année : 2017

Long‐term effects of systemic gene therapy in a canine model of myotubular myopathy

Matthew Elverman
  • Fonction : Auteur
Melissa Goddard
  • Fonction : Auteur
David Mack
  • Fonction : Auteur
Jessica Snyder
  • Fonction : Auteur
Michael Lawlor
  • Fonction : Auteur
Hui Meng
  • Fonction : Auteur
Alan Beggs
  • Fonction : Auteur
Karine Poulard
  • Fonction : Auteur
Anthony Marsh
  • Fonction : Auteur
Robert Grange
  • Fonction : Auteur
Valerie Kelly
  • Fonction : Auteur
Martin Childers
  • Fonction : Auteur

Résumé

ABSTRACT Introduction 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

Dates et versions

hal-04481605 , version 1 (28-02-2024)

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Citer

Matthew Elverman, Melissa Goddard, David Mack, Jessica Snyder, Michael Lawlor, et al.. Long‐term effects of systemic gene therapy in a canine model of myotubular myopathy. Muscle & Nerve, 2017, 56 (5), pp.943-953. ⟨10.1002/mus.25658⟩. ⟨hal-04481605⟩
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