A CNS-Directed, AAV9 Gene Therapy Restores Expression and Biochemical Function of Guanidinoacetate Methyltransferase in Models of GAMT Deficiency.

ABSTRACT: Guanidinoacetate methyltransferase (GAMT) is an essential enzyme in the biosynthesis of creatine, an important molecule in energy recycling. GAMT loss of function leads to GAMT deficiency (GAMT-D), an autosomal recessive disorder resulting in low creatine levels and the accumulation of a toxic intermediate, guanidinoacetate (GAA). GAMT-D patients present with intellectual disability and epilepsy, emphasizing the detrimental consequences of disturbed creatine metabolisms in the central nervous system (CNS). Current treatments are not curative and may not restore creatine metabolism in the brain. Here, we present a proof-of concept study testing the first CNS-directed, Adeno-associated virus serotype 9 (AAV9)-based gene therapy for the treatment of GAMT-D. the delivery of GAMT constru

SUBMITTER: Binsfeld R 

PROVIDER: S-EPMC12842229 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature