Nature Medicine：靶向少突胶质细胞的AAV基因疗法，治疗儿童遗传性脑病

Core Viewpoint - Canavan disease is a rare, hereditary neurodegenerative disorder characterized by severe physical and intellectual disabilities, typically manifesting symptoms between 3 to 6 months of age. The disease is caused by mutations in the ASPA gene, leading to toxic accumulation of N-acetylaspartate (NAA) in the brain, which adversely affects myelin development and function [2][5]. Group 1: Clinical Trial Overview - A phase 1/2 clinical trial was conducted to evaluate the safety and early efficacy of a novel recombinant adeno-associated virus vector, rAAV-Olig001, targeting oligodendrocytes for the treatment of Canavan disease [3][5]. - The trial involved 8 participants (5 male and 3 female), who received an intracranial administration of 3.7×10^13 vg of rAAV-Olig001-ASPA (MYR-101) [5]. Group 2: Safety and Efficacy Results - Among the 8 participants, 7 (87.5%) experienced at least one serious adverse event, none of which were deemed related to MYR-101, and all adverse events were resolved [6]. - The treatment resulted in a significant reduction in NAA concentration in cerebrospinal fluid, increased myelination, and improved developmental outcomes as measured by the Mullen Scales of Early Learning (MSEL) [6][7]. Group 3: Implications for Future Research - The reduction in NAA levels and increased myelination suggest successful targeting of oligodendrocytes by the AAV gene therapy, which may pave the way for similar gene therapy strategies for other demyelinating and metabolic brain diseases [7].