Neonatal gene therapy achieves sustained disease rescue of maple syrup urine disease in mice.

ABSTRACT: Maple syrup urine disease (MSUD) is a rare recessively inherited metabolic disorder causing accumulation of branched chain amino acids leading to neonatal death, if untreated. Treatment for MSUD represents an unmet need because the current treatment with life-long low-protein diet is challenging to maintain, and despite treatment the risk of acute decompensations and neuropsychiatric symptoms remains. Here, based on significant liver contribution to the catabolism of the branched chain amino acid leucine, we develop a liver-directed adeno-associated virus (AAV8) gene therapy for MSUD. We establish and characterize the Bckdha (branched chain keto acid dehydrogenase a)^-/- mouse that exhibits a lethal neonatal phenotype mimicking human MSUD. Animals were treated at P0 with intraven

SUBMITTER: Pontoizeau C 

PROVIDER: S-EPMC9174284 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature