IPSC-derived neural precursor cells engineering GBA1 recovers acid β-glucosidase deficiency and diminishes α-synuclein and neuropathology.

ABSTRACT: Mutations in GBA1, encoding the lysosomal acid β-glucosidase (GCase), cause neuronopathic Gaucher disease (nGD) and promote Parkinson disease (PD). The mutations on GBA1 include deletion and missense mutations that are pathological and lead to GCase deficiency in Gaucher disease. Both nGD and PD lack disease-modifying treatments and are critical unmet medical needs. In this study, we evaluated a cell therapy treatment using mouse iPSC-derived neural precursor cells (NPCs) engineered to overexpress GCase (termed hGBA1-NPCs). The hGBA1-NPCs secreted GCase that was taken up by adjacent mouse Gba ^-/- neurons and improved GCase activity, reduced GCase substrate accumulation, and improved mitochondrial function. Short-term in vivo effects were evaluated in

SUBMITTER: Peng Y 

PROVIDER: S-EPMC10102010 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature