Galactosylceramidase (GALC) (GALC)

Galactosylceramidase (GALC) is a lysosomal enzyme essential for the degradation of galactosylceramide and galactosylsphingosine (psychosine), which are key components of the myelin sheath (UniProt P54803). Deficiency of this enzyme, caused by mutations in the GALC gene, results in Krabbe disease, a fatal neurodegenerative disorder characterized by the accumulation of toxic psychosine and subsequent widespread demyelination (NIH GARD). Gene replacement therapy utilizing an AAVrh10 vector is an investigational approach designed to deliver a functional copy of the GALC gene to the central and peripheral nervous systems (PubMed: 33161454). By restoring GALC activity, the therapy aims to clear accumulated substrates, prevent further neurodegeneration, and stabilize myelin. The AAVrh10 serotype is specifically chosen for its high tropism for the central nervous system and its ability to achieve widespread distribution in neural tissues. Clinical development of these therapies, such as FBX-101 and OAV-101, involves monitoring psychosine levels as a primary biomarker of biochemical efficacy and assessing neurological milestones in affected patients (ClinicalTrials.gov: NCT04771416).

Other names

GalactocerebrosidaseGalactocerebroside beta-galactosidaseGALCERaseGalactosylceramide beta-galactosidase

Gene replacement therapy via AAVrh10 vector-mediated delivery of a functional GALC transgene to restore lysosomal galactosylceramidase activity and reduce toxic psychosine accumulation.