PR001 is an experimental gene therapy for neuronopathic Gaucher disease, primarily type 2 but also type 3 disease. Prevail Therapeutics — recently acquired by Eli Lilly — oversaw initial development of this treatment.

PR001 is given as a one-time intracisternal injection, or an injection directly into the cisterna magna — an area above the spinal canal and below the cerebellum.

How does PR001 work?

Mutations in the GBA1 gene are what cause Gaucher disease. This gene contains the instructions necessary for the production of the beta-glucocerebrosidase enzyme. This enzyme is responsible for the breakdown of molecules called glucocerebrosides. When there are mutations in the GBA1 gene, the beta-glucocerebrosidase enzyme does not work correctly and glucocerebroside builds in the nervous system and other organs, causing damage and leading to the symptoms of Gaucher disease.

PR001 is a gene therapy that aims to deliver a working copy of the GBA1 gene to the cells of the central nervous system (brain and spinal cord) in order to restore beta-glucocerebroside enzyme levels. It uses a harmless adeno-associated virus (AAV) to carry the working copy of the gene into cells.

Preclinical studies in animal models of Gaucher disease showed that PR001 was well-tolerated, and resulted in an increase in the beta-glucocerebrosidase enzyme and a decrease in glucocerebroside molecules in nerve cells, as well as better motor function.

PR001 in clinical trials

Researchers are now investigating PR001 in an open-label Phase 1/2 clinical trial (NCT04411654) called PROVIDE. The study is currently recruiting up to 15 children with type 2 Gaucher disease, ages up to 2 in New York. Locations in California, Minnesota, and Pennsylvania are expected to start recruiting soon. All participants will be given a single intracisternal injection of PR001. Investigators will then monitor the children for about five years. Patients will also receive corticosteroids and sirolimus, a medication to prevent rejections with transplants.

During the first year after injection, investigators will evaluate the safety and tolerability of PR001. They will also assess the efficacy and the effect on immunogenicity (the ability to trigger an immune response) of the treatment, as well as certain biomarkers. Finally, they will monitor safety and neurological outcomes, such as changes in cognitive function and motor development, for about four years. The study is expected to finish in April 2028.

Other information

The U.S. Food and Drug Administration granted PR001 fast track designation in October 2020. The agency also designated it an orphan drug and rare pediatric disease treatment.

Researchers are also investigating PR001 to treat Parkinson’s disease patients who have at least one GBA1 mutation in a Phase 1/2 clinical trial (NCT04127578) called PROPEL.

 

Last updated: Dec. 21, 2020

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Gaucher Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Brian holds a Ph.D. in Biomedical Engineering from Case Western Reserve University and a Bachelors of Science in Biomedical Engineering from Georgia Institute of Technology. He has co-authored numerous scientific articles based on his previous research in the field of brain-computer interfaces and functional electrical stimulation. He is also passionate about making scientific advances easily accessible to the public.
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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.
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Brian holds a Ph.D. in Biomedical Engineering from Case Western Reserve University and a Bachelors of Science in Biomedical Engineering from Georgia Institute of Technology. He has co-authored numerous scientific articles based on his previous research in the field of brain-computer interfaces and functional electrical stimulation. He is also passionate about making scientific advances easily accessible to the public.
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