PR001 in development by Prevail Therapeutics
Prevail Therapeutics, a wholly-owned subsidiary of Eli Lilly and Company, is developing an investigational gene therapy called PR001 that has the potential to slow or stop the underlying disease process in patients with neuronopathic Gaucher disease (nGD) and Parkinson’s disease with GBA1 mutations (PD-GBA).
Gaucher disease patients have mutations in both copies of a gene called GBA1. The GBA1 gene contains the instructions for making the protein beta-glucocerebrosidase, or GCase. GCase works in a compartment inside of cells called the lysosome, where it is responsible for the disposal and recycling of glycolipids (a type of fat). When there is an insufficient amount of active GCase, the lysosome does not function normally, which can lead to the symptoms seen in Gaucher disease, including nGD.
In order to deliver a healthy copy of the GBA1 gene to cells of the brain, PR001 uses a viral vector (or shuttle) called AAV9. AAV9 is a well-studied vector used by a number of companies developing gene therapy products, particularly those that target disorders of the nervous system. The therapy is designed to enable brain cells to produce enough active GCase for lysosomes to do their jobs and potentially slow or stop the disease from progressing.
In clinical trials, PR001 is administered by a one-time injection into the cerebrospinal fluid space in an area above the spinal cord called the cisterna magna. This type of injection is a direct, non-surgical technique that has been used safely for other purposes for many years.
Type 2 (neuronopathic) Gaucher disease
Gaucher disease has three types, which vary by severity of symptoms, age of onset and the presence of symptoms that affect the brain. Type 2 and Type 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by symptoms that affect the brain.
Type 2 Gaucher disease, the most severe form, affects infants. It causes rapid, progressive and irreversible brain damage usually beginning in the first six months of life; children typically die by age two. Patients with Type 2 Gaucher disease are also affected by the symptoms of Gaucher disease that occur throughout the body, such as spleen and liver enlargement and blood abnormalities.
Prevail is recruiting patients for PROVIDE, a Phase 1/2 clinical trial designed to evaluate the safety and effects of PR001 in infants 0-24 months of age with Type 2 Gaucher disease. Fifteen study participants are sought for this trial that will be conducted at several clinical sites.
with questions or to express interest in study participation.