Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.

ABSTRACT: Globoid cell leukodystrophy (GLD) is a fatal lysosomal storage disorder caused by a deficiency in the β-galactosylceramidase (GALC) enzyme, leading to severe demyelination and neurodegeneration, and often death before the age of 2 years. Hematopoietic stem/progenitor cell transplantation (HSPC-T) has limited efficacy due to inadequate GALC delivery to the central (CNS) and peripheral nervous systems (PNS) and associated risks. In vivo gene therapy (GT) using adeno-associated viral vectors shows promise, but safety concerns persist. This research presents a strategy using lentiviral (LV) vector-mediated ex vivo HSPC-GT with a chimeric GALC enzyme that incorporates peptides from α-l-iduronidase (IDUA) and apolipoprotein E II (APO) to enhance expression and blood-brain barrier penetration. Th

SUBMITTER: Cascino F 

PROVIDER: S-EPMC12703158 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature