VQ-101, targeting GBA gene mutations, to enter clinical testing
Experimental therapy designed to act as an allosteric activator of GCase
Vanqua Bio will initiate clinical development of VQ-101 — a small molecule capable of penetrating the brain — in the first quarter of 2024, the company announced. The clinical testing will involve both healthy volunteers and individuals with Parkinson’s disease associated with mutations in the GBA gene.
To help the company as it advances VQ-101 into clinical trials, Vanqua Bio also has expanded its leadership team with people who have “extensive expertise in rare diseases and neurodegenerative disorders, and bring first-hand knowledge of what it takes to translate cutting-edge science into breakthrough therapies that can transform patient care and outcomes,” said Jim Sullivan, PhD, Vanqua’s CEO.
Mutations in GBA are the most common genetic cause of Parkinson’s. Patients carrying these type of mutations often progress into more advanced disease stages faster and at a younger age than those with idiopathic (of unknown cause) Parkinson’s.
The GBA gene provides instructions for making glucocerebrosidase (GCase), an enzyme that helps break down a molecule called glucocerebroside into simpler sugars and fats in lysosomes, cells’ recycling centers.
When GBA is mutated, the activity of GCase is reduced, which causes the lysosomes to go awry. As a result, toxic forms of proteins, including alpha-synuclein, build up into clumps. Toxic alpha-synuclein clumping in nerve cells is a hallmark of Parkinson’s.
VQ-101 is designed to act as an allosteric activator of GCase, that is, a small molecule that binds to the enzyme and increases its activity. By doing this, VQ-101 is expected to restore lysosomes’ function and prevent alpha-synuclein from building up and damaging nerve cells.
VQ-101 activates wild-type, mutant forms of GCase in preclinical studies
In preclinical studies in patient-derived nerve cells, VQ-101 was seen to activate both wild-type (healthy) and mutant forms of GCase. It also prevented the accumulation of toxic forms of alpha-synuclein, according to the company.
Activation of GCase by VQ-101 was confirmed on blood samples drawn from healthy volunteers and people with Parkinson’s linked to GBA mutations. In four animal species, daily dosing led to significant levels of VQ-101 in the brain and spinal cord.Â
VQ-101 was found to be safe and well tolerated in preclinical studies, and is expected to be administered once daily in a planned first-in-human clinical trial testing VQ-101’s safety and ability to bind to the GCase enzyme, according to the company.
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