AAV9 gene therapy optimization for SMARD1/CMT2S: safety and long-term efficacy comparison of two vectors in a SMARD1 preclinical model.

ABSTRACT:

Background

Mutations in the Immunoglobulin Mu DNA Binding Protein 2 (IGHMBP2) gene cause Spinal Muscular Atrophy with Respiratory Distress type 1 (SMARD1), a rare, infantile, and fatal motor neuron disease, as well as the milder Charcot-Marie-Tooth disease type 2S (CMT2S). Gene therapy has emerged as a promising approach to correcting IGHMBP2 loss in SMARD1 models, but critical challenges remain.

Methods

In this study, we compared the efficacy of two novel, optimized adeno-associated virus 9 (AAV9)-IGHMBP2 vectors, utilizing either the Chicken β-Actin (CBA) or a truncated form of the methyl-CpG-binding protein 2 (MeCP2) promoter (P546), in the SMARD1 murine model via intracerebroventricular delivery. Treated mice survival, histopathological and molecular profile were analyze

SUBMITTER: Pagliari E 

PROVIDER: S-EPMC12765291 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature