Enrollment in the Phase 1/2 PROPEL trial, evaluating the safety, tolerability, and early efficacy of PR001 — a one-time gene therapy — for Parkinson’s disease associated with mutations in the GBA1 gene, is progressing at two centers in New York and patient dosing is continuing.
Prevail Therapeutics, which is developing the therapy, expects to present early interim results in the second half of 2020.
This first in-human study (NCT04127578) of PR001 expects to enroll 16 people with moderate-to-severe Parkinson’s with confirmed GBA1 mutations. More information on locations and contacts can be found at the trial’s page here; additional study locations are expected in Chicago and New York.
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 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 to 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 symptoms caused by the mutations in the GBA1 gene.
The investigational therapy was well-tolerated in preclinical studies in mice and primates with Parkinson’s disease. PR001 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.
In this double-blind Phase 1/2 trial, participants will be randomly assigned to receive two escalating doses of PR001 — a low and a high dose — or placebo, given as a single injection. The gene therapy is injected directly into one of the subarachnoid cisterns, or brain chambers filled with cerebrospinal fluid (CSF), which surrounds the brain and spinal cord.
The study will run for five years. During the first year, the researchers will assess PR001‘s safety and tolerability, and its impact on biomarkers of disease activity in the CSF and clinical efficacy measures. One specific biomarker the team will exam are changes in GCase enzyme activity levels in the blood and CSF.
Participants in the trial will continue to be followed for an additional four years after its conclusion to monitor safety as well as selected biomarkers and efficacy measures.
An update on the trial’s clinical progress was presented recently at the Cowen & Co. Annual Healthcare Conference in Boston.
The U.S. Food and Drug Administration granted fast track designation to PR001 in July 2019 for the treatment of people with Parkinson’s disease associated with GBA1 gene mutations. This designation accelerates a 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.
“We believe the PROPEL trial makes PR001 the first potentially disease-modifying gene therapy for PD-GBA patients to enter clinical trials,” Asa Abeliovich, MD, PhD, founder and CEO of Prevail, said in a press release.
“Its ongoing progress brings us a step closer to new treatment options for patients living with PD-GBA,” Abeliovich said. “We are excited about the potential of PR001 to slow or stop disease progression for PD-GBA patients.”
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