AAV9/SLC6A1 gene therapy rescues abnormal EEG patterns and cognitive behavioral deficiencies in Slc6a1-/- mice.

ABSTRACT: The solute carrier family 6 member 1 (SLC6A1) gene encodes the γ-aminobutyric acid (GABA) transporter GAT-1, the deficiency of which is associated with infantile encephalopathy with intellectual disability. We designed 2 AAV9 vectors, with either the JeT or MeP promoter, and conducted preclinical gene therapy studies using heterozygous and homozygous Slc6a1-KO mice at different developmental ages and various routes of administration. Neonatal intracerebroventricular administration of either vector resulted in significantly normalized EEG patterns in Slc6a1-/- or Slc6a1+/- mice as well as improvement in several behavioral phenotypes of Slc6a1-/- mice. However, some mortality and adverse effects were observed in neonatal-treated mice. Intrathecal administration of either vector at P5 normali

SUBMITTER: Guo W 

PROVIDER: S-EPMC11785923 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature