News in Context: Clinical Trial Results for GBA1-Targeted Parkinson’s Therapy

Parkinson's is a complex disease that results from different biological factors, such as variations in genes, as well as environmental influences and aging. Variations in the GBA1 gene are among the most common genetic changes associated with Parkinson's. These changes reduce the activity of an enzyme called glucocerebrosidase (GCase), which helps remove cellular waste from the brain. This leads to the toxic buildup of proteins linked to Parkinson's and other related conditions. Because of this, drugs that target GBA1 and its underlying GCase activity are promising Parkinson's therapeutics.

A clinical trial into one of those drugs, BIA 28-6156 (pariceract), reported its findings this week. While the drug had no safety concerns, participants who received the drug had similar disease progression when compared to study participants in the control group. (Disease progression was measured by changes in movement scores over time. Movement was measured by clinicians and by participants or care partners using a common benchmark called the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, or MDS-UPDRS.)

As a result of the findings, Bial decided that it will not continue studying this drug for GBA1-related Parkinson's.

About the ACTIVATE Trial

ACTIVATE was a Phase II clinical study testing BIA 28-6156 (pariceract) in a group of people with GBA1-linked Parkinson's. The study, led by the company Bial, is considered an early pioneer in the field of Parkinson's precision medicine; BIA 28-6156 was designed to bind to GCase and enhance its enzyme activity, and it was being tested in people with GBA1 gene variations.

The study enrolled 273 participants across 85 clinical sites in 11 countries throughout Europe and North America. Participants were divided into three groups and received one of two doses (10mg or 60mg) of the daily, oral drug or were assigned to the placebo (control) over the course of 18 months.

Research Continues into GBA1 Therapies

ACTIVATE tested just one potential strategy for addressing GBA1 biology in Parkinson's disease. Several therapies in development for GBA1-associated Parkinson's, including studies in Phase I and Phase III, are looking at different ways to activate, stabilize or restore GCase. These collective efforts underscore the importance of diversifying the therapeutic pipeline, leaving no stone unturned for our Parkinson's community. In fact, these advancements would not be possible without the individual contributions of Parkinson's volunteers, family, study site staff and other supporters who make clinical research possible.

Findings from ACTIVATE will also provide a key evidence base to inform and strengthen ongoing and future studies. The company announced that more data are expected to be shared with the Parkinson's community through future scientific presentations and publications.

Advancing GBA1 Research

The Foundation's work spans the full spectrum of therapeutic development, from supporting early-stage research to de-risking promising drug targets. Just a few weeks ago, the Foundation joined with other funders to launch the GBA1 Parkinson's Disease Research Catalyst Program. This program aims to advance understanding of what happens in the brain and body because of GBA1 variations - insights that can guide GBA1-focused therapeutic development while also strengthening the broader search for better treatments, and a cure, for all people living with Parkinson's.

• Linda Huynh, Ph.D.

  Lead Research Editor