AAV1.NT-3 gene therapy in a CMT2D model: phenotypic improvements in Gars^P278KY/+ mice.

ABSTRACT: Glycyl-tRNA synthetase mutations are associated to the Charcot-Marie-Tooth disease type-2D. The Gars^P278KY/+ model for Charcot-Marie-Tooth disease type-2D is known best for its early onset severe neuropathic phenotype with findings including reduced axon size, slow conduction velocities and abnormal neuromuscular junction. Muscle involvement remains largely unexamined. We tested the efficacy of neurotrophin 3 gene transfer therapy in two Gars mutants with severe (Gars^P278KY/+ ) and milder (Gars^ΔETAQ/+ ) phenotypes via intramuscular injection of adeno-associated virus setoype-1, triple tandem muscle creatine kinase promoter, neurotrophin 3 (AAV1.tMCK.NT-3) at 1 × 10¹¹ vg dose. In the Gars^P278KY/+ mice, the tr

SUBMITTER: Ozes B 

PROVIDER: S-EPMC8568849 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature