Type 2 Gaucher Trial of PR001 Gene Therapy Has Hold Lifted by FDA – Gaucher Disease News

The U.S. Food and Drug Administration (FDA) has lifted the clinical hold on a Phase 1/2 trial designed to test the gene therapy candidate PR001 in patients with type 2 Gaucher disease.

The team atPrevail Therapeutics expects to initiate patient dosing in the first half of 2020.

Prevail was awaiting a decision by the FDA to test higher doses of PR001 than initially planned. This request was supported by preclinical evidence of greater efficacy with no safety issues at such dosages. The investigational new drug (IND) application of PR001, an essential step to opening a clinical study, had first been accepted in June 2019.

PR001 uses a modified, harmless version of an adeno-associated virus (AAV9) to deliver a fully working version of the GBA1 gene to nerve cells. Mutations in this gene cause Gaucher disease by producing a defective enzyme called beta-glucocerebrosidase, which leads to the accumulation of fatty molecules inside cells.

In type 2 Gaucher disease, called acute infantile neuronopathic Gaucher disease, these toxic fatty molecules build up in the patients brain from early infancy, resulting in neurological symptoms.

By restoring production of normal beta-glucocerebrosidase in affected brain cells, a single dose of PR001 is intended to ease Gaucher symptoms and modify disease course.

Work in mice and monkeys showed that PR001 now being developed in collaboration with Lonza Pharma & Biotech is well-tolerated, leads to the production of a functional enzyme in nerve cells, reduces the accumulation of fatty molecules, and improves motor function.

We are pleased to now have an active IND for PR001 for the nGD [neuronopathic Gaucher disease] indication and look forward to initiating a Phase 1/2 clinical trial in the first half of 2020, Asa Abeliovich, MD, PhD, Prevails founder and CEO, said in a press release.

Patients with nGD have the most severe form of Gaucher disease and a significant unmet need for therapies to treat their neurological manifestations. We believe PR001 has tremendous potential, he added.

In addition, the company plans to initiate another Phase 1/2 study in people with type 3 Gaucher later this year. Patients with this type also experience neurological symptoms, but they are milder and progress slower than those seen in patients with type 2 Gaucher.

Prevail is also developing PR001 for GBA1 mutation-related Parkinsons disease. Mutations in the GBA1 gene are one of the most common genetic risk factors for Parkinsons. A Phase 1/2 clinical trial (NCT04127578), called PROPEL, is currently recruiting participants with Parkinsons to test PR001 administered directly into the cerebrospinal fluid (the liquid surrounding the brain and spinal cord).

With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.

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Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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Type 2 Gaucher Trial of PR001 Gene Therapy Has Hold Lifted by FDA - Gaucher Disease News