VQ-101 restores enzyme lacking in GBA-linked Parkinson’s: Early trial
GCase activity boosted by more than 70% in patients with GBA gene mutations
The experimental oral therapy VQ-101 can successfully restore a critical cellular function in people with a genetic form of Parkinson’s disease, the treatment’s developer, Vanqua Bio, has announced.
One month of daily treatment with VQ-101 safely and robustly boosted the activity of the glucocerebrosidase (GCase) enzyme in patients carrying GBA gene mutations, according to interim data from an early clinical trial. The GBA gene is one of the most common genetic causes of Parkinson’s. Its mutations impair the GCase enzyme, leading to a toxic buildup of proteins in the brain.
The ongoing Phase 1a/1b clinical trial is evaluating VQ-101 against a placebo in healthy volunteers and Parkinson’s patients with and without GBA mutations.
“We are pleased to announce that VQ-101 demonstrated robust activation of … GCase and full [brain and spinal cord] penetrance at doses that were safe and well tolerated following 28 days of dosing in patients with GBA-PD [GBA-linked Parkinson’s disease],” Jim Sullivan, PhD, CEO of Vanqua Bio, said in a company press release.
Mechanism of GCase activation
Parkinson’s patients who completed the one-month treatment period had the option to continue or start treatment with VQ-101 for six months in the trial’s open-label extension portion.
“These results support the continued development of VQ-101 in Parkinson’s disease, and we look forward to sharing additional data from the open-label extension portion of the study in 2026,” Sullivan said.
The findings were shared at the 2025 International Congress of Parkinson’s Disease and Movement Disorders in a presentation, titled “VQ-101, a CNS-Penetrant Small Molecule Allosteric Activator of Glucocerebrosidase (GCase), Demonstrates Favorable Tolerability and Sustained Activation of Lysosomal GCase in Individuals with Parkinson’s Disease.”
The GBA gene provides instructions to produce GCase, an enzyme that helps break down the fatty molecule glucocerebroside inside lysosomes, or the cells’ recycling centers.
GBA mutations, one of the most common genetic causes of Parkinson’s, reduce GCase activity and impair lysosomal function. This results in the accumulation of toxic protein clumps inside nerve cells, particularly clumps composed of the alpha-synuclein protein, a Parkinson’s hallmark.
VQ-101 is an oral small molecule designed to reach the brain and alter the shape of GCase, thereby boosting its activity. Its goal is to restore lysosomal function and prevent alpha-synuclein clumping, thereby reducing nerve cell damage.
Based on positive preclinical data, Vanqua Bio announced plans to move VQ-101 into clinical testing. In the ongoing, Phase 1a/1b clinical trial, 90 healthy volunteers and 70 Parkinson’s patients, with and without GBA mutations, were randomly assigned to receive the experimental therapy or a placebo. Dosing began last year, the company announced in April.
Results from the trial’s Phase 1a portion, which involved only healthy volunteers, showed VQ-101 safely boosted GCase activity by more than 75%. Also, the therapy was detected at high levels in their cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, confirming its ability to reach the brain.
Newly announced results are for participants with GBA-related Parkinson’s, in the study’s Phase 1b portion, where they received one of several VQ-101 doses or a placebo, once daily for 28 days.
VQ-101 boosted GCase activation in a dose-dependent manner, exceeding the target engagement goal of 50% at all doses, and resulting in more than 70% activation of GCase. Reaching an activation level of 50% is expected to restore patients’ GCase activity to levels seen in healthy people.
“By restoring GCase activity to at least healthy volunteer levels, we believe that VQ-101 has the potential to positively impact the lives of patients following longer term dosing,” Sullivan said.
The experimental oral therapy was also found in the blood and CSF at levels that support once daily oral dosing. Drug exposures rose with increasing doses, and were not influenced by food intake.
Safety and progression data
VQ-101 was generally safe and well tolerated, with no reports of serious adverse events or discontinuations due to adverse events. All adverse events were reported as mild or moderate in severity.
“These results, together with preclinical data, support the potential for VQ-101 to slow or stop the progression of [Parkinson’s disease] by increasing GCase activity and blocking the accumulation of misfolded [alpha-synuclein],” the researchers wrote in the submitted abstract for the presentation.
In a second presentation, titled “Decline in Motor Function and Cognitive Abilities in GBA PD Compared to Idiopathic PD (iPD),” Vanqua reported data comparing changes in the motor and cognitive function between 75 Parkinson’s patients with GBA mutations and 75 patients without such mutations who were matched by age, sex, disease severity, and duration.
The researchers used data from the Michael J. Fox Foundation’s Parkinson’s Progression Markers Initiative database. Results showed the time to worsening of motor function and cognitive abilities was shorter in patients with GBA mutations compared with those without these mutations.
“It remains critical to measure and find treatments for rapidly progressing motor and cognitive decline in GBA PD patients,” the researchers wrote.
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