Work

Faster disease progression in Parkinson's disease with glucocerebrosidase genotype: But not apparent immediate from diagnosis

Year: 2025

Type: article

Abstract: Background This study presents post-hoc analyses of the LEAP study focusing on disease progression in patients with early Parkinson's disease (PD) who either have a glucocerebrosidase gene ( GBA1 ) mutation (GBA1mut) or do not have a mutation (GBA1wt) over a period of up to five years. Objective To investigate the difference in disease progression between GBA1mut and GBA1wt over 80 weeks and five years. Methods The study analyzed the difference in disease progression between GBA1mut and GBA1wt using the UPDRS and its subscales, Levy A and B scores, and the difference in levodopa equivalent daily dose (LEDD) over 80 weeks and five years, with mixed-effects regression models. Results The GBA1 mutation carrier status was determined in 394 patients, with 52 being GBA1mut and 342 being GBA1wt. From baseline to 80 weeks, the change in total UPDRS score was similar for GBA1mut and GBA1wt (difference 1.7 points in favor of GBA1mut, p = 0.38). From baseline to five years, GBA1mut had 5.9 points (p = 0.04) more worsening of total UPDRS compared to GBA1wt and GBA1mut had 1.0 point (p = 0.02) more deterioration in UPDRS subscale IV, related to therapy complications, compared to GBA1wt. There were no significant between-group differences in changes in UPDRS subscales, Levy A and B scores, and LEDD. Conclusions These findings suggest that over the long term, PD patients with a GBA1 mutation experience faster disease progression compared to those without a GBA1 mutation, although this difference in progression was not apparent within the initial 80 weeks of the trial.

Source: Journal of Parkinson s Disease

DOI: 10.1177/1877718x251361507