AAN 2026: VQ-101 reaches the brain, hits target in diverse Parkinson’s patients
Enzyme activity returns to levels seen in healthy volunteers in Phase 1 study
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- VQ-101 is an oral therapy for Parkinson's, targeting GCase to clear toxic proteins and prevent neurodegeneration.
- Phase 1 trial data show it reached the brain, increasing GCase activity more than 75% in patients with and without GBA mutations.
- The therapy was well tolerated with mild side effects, supporting further clinical trials for Parkinson's.
A new experimental oral therapy called VQ-101 successfully reached the brain and increased the activity of a key protective protein in people with Parkinson’s disease, according to early trial results. The Phase 1 study showed that the treatment, developed by Vanqua Bio, effectively boosted protein levels in patients with and without GBA gene mutations.
These findings were presented by Maurizio Facheris, MD, chief medical officer of Vanqua Bio, at the American Academy of Neurology Annual Meeting, held April 18-22 in Chicago and online. Facheris noted that the data provide a strong foundation for moving the treatment into more advanced clinical trials.
His talk, titled “The small molecule VQ-101 demonstrates sustained lysosomal glucocerebrosidase (GCase) activation in idiopathic Parkinson’s disease,” highlighted the therapy’s ability to maintain high levels of enzyme activity over time.
Restoring the cell’s recycling center
In Parkinson’s disease, progressive nerve cell death is linked to the toxic accumulation of the alpha-synuclein protein. Lysosomes, the cellular recycling centers that break down old or faulty proteins, can’t efficiently clear harmful protein clumps.
Glucocerebrosidase (GCase) is an enzyme involved in breaking down certain fatty molecules within lysosomes. Mutations in GBA, the gene that produces GCase, are the most common genetic risk factors for Parkinson’s. These mutations lower GCase activity, ultimately impairing lysosome function and contributing to toxic protein accumulation.
Even without GBA mutations, people with idiopathic Parkinson’s disease are found to have reduced GCase activity that may contribute to lysosome dysfunction and alpha-synuclein buildup.
As such, targeting GCase is a promising therapeutic approach for both GBA-associated and idiopathic forms of Parkinson’s. VQ-101 is an oral small molecule designed to enter the brain and increase GCase activity.
“Our hypothesis is that by restoring lysosomal function, we can block the accumulation of alpha-synuclein and eventually stop neurodegeneration,” Facheris said. He added that VQ-101 is designed to boost GCase activity “directly where it matters — in the lysosome.”
The Phase 1a/1b trial, which began dosing in 2024, is testing VQ-101 against a placebo in healthy volunteers and Parkinson’s patients, with and without GBA mutations.
In addition to safety, the study is evaluating the degree of GCase activation achieved. The goal was to reach at least 75% activation, as data from lab studies showed that this could almost completely block alpha-synuclein accumulation, according to Facheris.
In the Phase 1a part, which involved healthy volunteers, VQ-101 was well tolerated and increased GCase activity by more than 75%. More recently, data from participants with GBA-related Parkinson’s in the Phase 1b part showed that the therapy boosted GCase activity to levels seen in healthy people.
Facheris discussed additional data from trial participants with Parkinson’s disease, both with and without GBA mutations. Participants initially received daily VQ-101 (150 or 300 mg) or a placebo for about a month, followed by two optional open-label extension periods during which all received VQ-101.
Favorable safety and brain penetration
Across healthy volunteers and Parkinson’s patients dosed in the study, the therapy has shown a “very favorable safety profile,” according to the physician. The majority of side effects have been mild, and none have been serious.
In Parkinson’s patients, the medication reached high levels in the cerebrospinal fluid that surrounds the brain and spinal cord, suggesting that the therapy gets into the brain as intended.
VQ-101 led to dose-dependent increases in GCase activation that persisted for three months. On average, the lower dose achieved a 74% GCase activation, while the higher dose exceeded the desired 75% activation threshold. GCase activation was consistent with that of healthy volunteers and was similar in patients with and without GBA mutations.
Ultimately, VQ-101 could be a “best-in-class” treatment option for Parkinson’s disease, Facheris said. “We are the first ones to demonstrate an increase of GCase activity up to … or even more than 75% in the lysosome.”
Facheris noted that the data support additional studies of VQ-101 for the neurodegenerative disease. Vanqua is planning on a longer-term clinical trial that could be launched as early as next year.
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