GBA-associated PD: stratifying patients based on GBA variants

Glucocerebrosidase (GBA) mutations represent the largest known genetic risk factor for the development of Parkinson’s disease (PD), with 15 - 20% of patients with PD carrying a heterozygous GBA mutation. Enza Maria Valente, MD, PhD, IRCCS Mondino Foundation & University of Pavia, Pavia, Italy, outlines the clinical features of GBA-associated PD and the current research efforts to improve our understanding of the various phenotypes associated with different GBA variants. As not all individuals with a GBA mutation will develop PD, efforts are ongoing to understand how to predict disease onset in asymptomatic carriers. Several markers of disease conversion have been assessed. Additionally, there is also heterogeneity within individuals who do convert to GBA-associated PD. As larger cohorts have been assessed, there is increasing evidence to support a stratification of these patients based on the specific GBA variant present. Prof. Valente discusses the need to detailed characterization of genotype-phenotype correlations to enable accurate prognostication and to discover therapeutic strategies that may specifically tackle the pathogenetic mechanism underlying GBA dysfunction in order to prevent or delay disease progression. This interview took place during the 2021 International Congress of Parkinson's Disease and Movement Disorders.