AAV-mediated GBA1 and GDNF rescue neurological defects in a murine model of neuronopathic Gaucher disease.

ABSTRACT: Neuropathic Gaucher disease (nGD) is a life-threatening disease that progresses rapidly and is caused by a glucosylceramidase beta 1 (GBA1) mutation, which encodes the lysosomal hydrolase β-glucocerebrosidase (GCase). Nerve damage in nGD, associated with stunted growth and development, arises from the degeneration and death of nervous system cells, which is often irreversible. Approved therapies effectively reduce the substrate burden outside the central nervous system (CNS) through augmenting mutant enzyme activity with pharmacologic recombinant GCase or by inhibiting glucocerebroside synthesis. However, these therapies do not provide neuroprotection. In this study, we developed a novel double-gene therapy based on adeno-associated virus (AAV), AAV9-GBA1-GDNF, which stably e

SUBMITTER: Meng Y 

PROVIDER: S-EPMC11979523 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature