Prevail Therapeuticsis asking the U.S. Food and Drug Administration (FDA) to approved a request to open clinical trials, at higher doses than initially planned, into its investigational gene therapy PR001 in people with pediatric neuropathic Gauchers disease (type 2).

In its updated Investigational New Drug (IND) application, Prevail modified the original design of its clinical trial to allow for a higher starting dose of the therapy. This decision was based on conversations with the FDA and preclinical data supporting PR001 as a more effective and still safe treatment at higher doses, it announced in a press release.

The company is waiting on an FDA decision, and expects to start recruiting patients for a Phase 1/2 trial testing PR001 in children with neuropathic Gaucher in the first half of 2020. The IND, an essential step to opening a clinical study, was first filed in June.

We are dedicated to developing PR001 for pediatric nGD[neuropathic Gaucher disease], the most progressive form of Gaucher disease, which involves neurological manifestations that cause severe morbidity and mortality. We believe PR001 has tremendous potential to slow or stop disease progression in patients who currently have no disease-modifying therapeutic options, Asa Abeliovich, MD, PhD, founder, and CEO of Prevail, said in the release.

Gaucher disease is a hereditary condition caused by mutations in the GBA gene, which leads to the production of defective beta-glucocerebrosidase. This protein breaks down fatty molecules that are toxic if they accumulate inside the cells, leading to the array of symptomsassociated with Gauchers disease.

Toxic fatty molecules building in the brain lead to manifestations of neuropathic Gauchers, which can be observed from early infancy in type 2 disease.

PR001 uses a modified, harmless version of an adeno-associated virus (AAV9) to deliver a fullyworking copy of the GBA1 gene to nerve cells. This allows these cells to initiate processes that lead to the production of functional beta-glucocerebrosidase, which could ease the symptoms of neurotropic Gauchers disease. A single dose of PR001 has the potential to modify the disease with long-lasting effect.

Studies in mice and primatesfound that PR001 was well-tolerated and led to the expression of a functional protein in nerve cells, reducing the accumulation of fatty molecules and consequent symptoms.

AAV9 has been widely used to deliver gene therapies both in practice and in clinical trials. A transport vehicle for the corrected gene, it is engineered to be a harmless virus and can cross the blood-brain barrier, allowing it to reach nerve cells.

PR001 is also being developed and tested as a treatment of people with Parkinsons diseasewho have mutations in the GBA gene. Prevail has an open IND applicationfor trials here, and the therapy received fast-track designation by the FDA as a possible Parkinsons treatment.

Alejandra has a PhD in Genetics from So Paulo State University (UNESP) and is currently working as a scientific writer, editor, and translator. As a writer for BioNews, she is fulfilling her passion for making scientific data easily available and understandable to the general public. Aside from her work with BioNews, she also works as a language editor for non-English speaking authors and is an author of science books for kids.

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Ins Martins holds a BSc in Cell and Molecular Biology from Universidade Nova de Lisboa and is currently finishing her PhD in Biomedical Sciences at Universidade de Lisboa. Her work has been focused on blood vessels and their role in both hematopoiesis and cancer development.

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Type 2 Gaucher Trial of Gene Therapy PR001 May Open with Higher Dose - Gaucher Disease News