Rescue of myocytes and locomotion through AAV2/9-2YF intracisternal gene therapy in a rat model of creatine transporter deficiency.

ABSTRACT: Creatine deficiency syndromes (CDS), caused by mutations in GATM (AGAT), GAMT, and SLC6A8, mainly affect the central nervous system (CNS). CDS show brain creatine (Cr) deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy, and motor dysfunction. AGAT/GAMT-deficient patients lack brain Cr synthesis but express the Cr transporter SLC6A8 at the blood-brain barrier and are thus treatable by oral supplementation of Cr. In contrast, no satisfactory treatment has been identified for Cr transporter deficiency (CTD), the most frequent of CDS. We used our Slc6a8^Y389C CTD rat model to develop a new AAV2/9-2YF-driven gene therapy re-establishing the functional Slc6a8 transporter in rat CNS. We show, after intra-

SUBMITTER: Fernandes-Pires G 

PROVIDER: S-EPMC11091509 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature