We are developing potentially disease-modifying AAV9-based gene therapies for the treatment of genetically defined neurodegenerative diseases.
PD-GBA and Gaucher disease are driven by mutations in the same gene, called GBA1. This gene contains the instructions for making the lysosomal enzyme beta-glucocerebrosidase, or GCase, which is needed for the disposal and recycling of glycolipids — a type of cellular component that is known to accumulate with aging. PD-GBA patients have mutations in at least one chromosomal copy of GBA1, while Gaucher disease patients have mutations in both chromosomal copies. Without enough GCase, glycolipids accumulate, causing lysosomal dysfunction and aggregation of the protein α-Synuclein in cells, which we believe leads to the inflammation and neurodegeneration behind PD-GBA and neuronopathic Gaucher disease.
PR001 utilizes the well-studied viral vector AAV9 to deliver a healthy copy of the GBA1 gene. In our PROPEL and PROVIDE clinical trials, PR001 is administered by a one-time injection into an area above the spinal canal called the cisterna magna to treat the brain. The cisterna magna injection is a direct, non-surgical technique that has been used safely in humans for a century. In our PROCEED clinical trial, PR001 is administered as a single IV infusion to treat Gaucher disease Type 1.
The U.S. FDA has granted Fast Track designation for PR001 for the treatment of PD-GBA and for the treatment of Type 2 Gaucher disease. It has also granted Orphan Drug designation for PR001 for the treatment of patients with Gaucher disease, and Rare Pediatric Disease designation for the treatment of Type 2 Gaucher disease.
PR001 is currently being studied in three Phase 1/2 clinical trials. Our PROPEL trial is a Phase 1/2 clinical trial of PR001 for the treatment of patients with PD-GBA. Our PROVIDE trial is a Phase 1/2 clinical trial of PR001 for the treatment of Type 2 Gaucher disease. Our PROCEED trial is a Phase 1/2 clinical trial of PR001 for the treatment of Type 1 Gaucher disease. Our PROPEL and PROVIDE trials are currently recruiting.
PR006 is being developed as a potentially disease-modifying, single-dose gene therapy for patients with frontotemporal dementia with GRN mutations (FTD-GRN).
FTD-GRN is a rapidly progressing neurodegenerative disease caused by a lack of progranulin, a protein that is found both outside of brain cells and inside the cells, in the lysosomes. Healthy levels of progranulin are necessary for cellular processes such as lysosomal function, neuronal survival and normal activity of the microglia, a type of brain-based immune cell. In FTD-GRN patients, mutations in the gene GRN cause the body to produce insufficient progranulin. Without enough of the enzyme, the lysosomes cannot effectively degrade or recycle proteins. This leads to inflammation and neurodegeneration.
PR006 is designed to slow or stop disease progression in FTD-GRN patients by increasing progranulin levels via delivery of a healthy GRN gene into the central nervous system (CNS). Like PR001, PR006 is administered by injection into the cisterna magna, using the well-studied viral vector AAV9.
The U.S. FDA has granted Orphan Drug designation for the treatment of FTD and Fast Track designation for the treatment of FTD-GRN. The European Commission has granted orphan designation for PR006 for the treatment of FTD.
PR006 is currently being studied in our PROCLAIM trial, a Phase 1/2 clinical trial of PR006 for the treatment of patients with FTD-GRN.