AAV1.tMCK.NT-3 gene therapy improves phenotype in <i>Sh3tc2^-/-</i> mouse model of Charcot-Marie-Tooth Type 4C.

ABSTRACT: Charcot-Marie-Tooth Type 4C (CMT4C) is associated with mutations in the SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene, primarily expressed in Schwann cells (SCs). Neurotrophin-3 (NT-3) is an important autocrine factor for SC survival and differentiation, and it stimulates neurite outgrowth and myelination. In this study, scAAV1.tMCK.NT-3 was delivered intramuscularly to 4-week-old Sh3tc2^-/- mice, a model for CMT4C, and treatment efficacy was assessed at 6-month post-gene delivery. Efficient transgene production was verified with the detection of NT-3 in serum from the treated cohort. NT-3 gene therapy improved functional and electrophysiological outcomes including rotarod, grip strength and nerve conduction velocity. Qualitative and quantitative histopat

SUBMITTER: Ozes B 

PROVIDER: S-EPMC11562120 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature