Prevail Therapeutics will soon start its Phase 1/2 clinical trial evaluating the safety, tolerability, and early efficacy of its one-time gene therapy — called PR001 — for Parkinson’s disease associated with mutations in the GBA1 gene.
The trial is expected to enroll up to 16 people with confirmed GBA1 mutations. Participants will be randomly assigned to receive two escalating doses of PR001, or placebo, administered as a single injection.
The company expects that dosing will start during 2019.
“We are excited to begin dosing patients in our Phase 1/2 clinical trial for PD-GBA this year,” Asa Abeliovich, MD, PhD, founder and CEO of Prevail, said in a press release. “We believe PR001 has tremendous potential to slow or stop disease progression in patients with PD-GBA … who currently have no disease-modifying therapeutic options.”
People with GBA1 mutations have up to a five-fold higher risk of developing Parkinson’s disease. Indeed, estimates point to a link to GBA1 mutations in 7 to 10% of all Parkinson’s cases.
The GBA1 gene contains all the information necessary to produce the enzyme beta-glucocerebrosidase (GCase) — an important component of cells’ recycling factories, called lysosomes. Lack of this enzyme, or its faulty activity, will make cells accumulate toxic substances inside them, which may contribute to the neurodegeneration seen in Parkinson’s disease.
PR001 was designed as a single-dose gene therapy that will provide nerve cells with a fully working copy of the GBA1 gene. This new method uses a modified and harmless version of an adeno-associated virus (AAV9) to deliver the gene to cells, which will then be able to recover GCase function.
This gene therapy is expected to ease Parkinson’s disease symptoms triggered by the mutated gene.
Studies in mice and primates with Parkinson’s disease demonstrated that PR001 was well-tolerated. The gene therapy also was found to promote an increase in GCase enzyme activity, which resulted in reduced accumulation of toxic fatty molecules, and improvements in motor function.
The U.S. Food and Drug Administration (FDA) granted fast track designation to PR001 in July 2019 for the treatment of people with Parkinson’s disease associated with GBA1 gene mutations. The designation accelerates the therapy’s development and may help expedite its approval by providing more frequent meetings with the FDA and discussions about the therapy’s development plan.