Intrathecal delivery of a bicistronic AAV9 vector expressing β-hexosaminidase A corrects Sandhoff disease in a murine model: A dosage study.

ABSTRACT: The pathological accumulation of GM2 ganglioside associated with Tay-Sachs disease (TSD) and Sandhoff disease (SD) occurs in individuals who possess mutant forms of the heterodimer β-hexosaminidase A (Hex A) because of mutation of the HEXA and HEXB genes, respectively. With a lack of approved therapies, patients experience rapid neurological decline resulting in early death. A novel bicistronic vector carrying both HEXA and HEXB previously demonstrated promising results in mouse models of SD following neonatal intravenous administration, including significant reduction in GM2 accumulation, increased levels of Hex A, and a 2-fold extension of survival. The aim of the present study was to identify an optimal dose of the bicistronic vector in 6-week-old SD mice by

SUBMITTER: Ryckman AE 

PROVIDER: S-EPMC10777117 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature