GBA1-linked Parkinson’s disease

Gaucher disease is a rare, autosomal recessive disease caused by mutations in the GBA1 gene, which encodes the enzyme glucocerebrosidase.^4,5 This enzyme is required for the normal function of lysosomes – a component of the cell that degrades unwanted materials.^1,3,5 It was in the treatment of Gaucher disease that researchers noted that there were higher proportions of patients with PD than would otherwise be expected, highlighting GBA1 as a shared risk factor for both Gaucher disease and PD.⁴ The increasing understanding of GBA1-driven PD pathology has led to some promising avenues of treatment research, including the idea of using virus vectors to deliver wild-type glucocerebrosidase to neurons, and the use of small molecule chaperone proteins to increase the levels of properly folded glucocerebrosidase within cells.²

References:
1.GeneCards. GBA1. Available at: https://www.genecards.org/cgi-bin/carddisp.pl?gene=GBA1. Accessed September 2024.

2.Höglinger G, Schulte C, Jost WH, et al. GBA-associated PD: chances and obstacles for targeted treatment strategies. J Neural Transm (Vienna) 2022; 129 (9): 1219–1233.

3.Smith L, Schapira AHV. GBA variants and Parkinson disease: mechanisms and treatments. Cells 2022; 11 (8): 1261.

4.Riboldi GM, Di Fonzo AB. GBA, Gaucher disease, and Parkinson’s disease: from genetic to clinic to new therapeutic approaches. Cells 2019; 8 (4): 364.

5.Schapira AH. Glucocerebrosidase and Parkinson disease: recent advances. Mol Cell Neurosci 2015; 66 (Pt A): 37–42.