Our Science

Prevail Therapeutics is pioneering the development of novel gene therapies that target the root genetic causes of Parkinson’s disease, frontotemporal dementia, Alzheimer’s disease, ALS, and other neurodegenerative disorders.

We seek to treat patient populations with urgent unmet needs, who currently have no available therapies to modify the progressive course of their disease.

Leveraging recent breakthroughs in human genetics and the transformative success of AAV-based gene therapy, our goal is to use a precision medicine approach to slow or stop the progression of neurodegenerative diseases. Prevail is particularly focused on neurodegenerative diseases caused by lysosomal dysfunction; our hypothesis is that restoring healthy lysosomal function in the cells of a patient’s central nervous system could stop the progression of the patient’s neurodegenerative disease.

Our approach centers on selecting patient populations with particular genetic mutations whom we believe can be treated by increasing or decreasing the expression of a particular gene through gene therapy. Each of our gene therapy candidates is intended to be a one-time treatment to correct the key underlying genetic mutation that we believe drives disease progression.


Lysosomes are membrane-bound organelles found in all cells. Lysosomes serve as the cell’s “recycling center,” as enzymes within the lysosome act to degrade proteins, lipids and sugars that come in from the cell’s cytoplasm (through autophagic trafficking) or its exterior (through endosomal trafficking). Lysosomes play an especially critical role in long-lived cells, such as neurons, and in the aging process. Deficiencies in various lysosomal enzymes can induce the accumulation of toxic materials in the cells, resulting in toxicity and inflammation, which we believe causes neurodegenerative disease.

Mutations in Lysosomal Genes Cause Lysosomal Dysfunction Leading to Toxicity, Inflammation and Neurodegenerative Disease

Human genetic studies have identified genes that are highly associated with several neurodegenerative diseases, including Parkinson’s disease. Many of these genes are known to play a role in lysosomal function and trafficking.

Our hypothesis is that restoring healthy lysosomal function in the cells of a patient’s central nervous system will slow or stop the progression of neurodegenerative disease.

Gene Therapy

Gene therapy breakthroughs present new hope for patients with neurodegenerative diseases. Over the past decades, simply reaching the intended target was a major challenge for any neurological drug, due in part to the presence of the blood-brain barrier. Advances in gene therapy technology allow for the efficient and widespread delivery of gene therapies to the central nervous system.

Prevail is developing adeno-associated virus (AAV)-based gene therapies for the treatment of neurodegenerative diseases. AAVs are small, non-replicating viruses that are not known to cause disease in humans. AAVs can be used as shuttle vectors to deliver engineered DNA (transgene) cargos to human cells. AAV-based vectors have shown substantial promise in achieving stable, long-lasting transgene expression.

We have chosen to use AAV9 for our initial programs based on its transformational biological properties and track record. AAV9 is uniquely well-suited to deliver genetic material to the brain, and has demonstrated efficacy, acceptable safety, and broad brain-wide biodistribution in third-party clinical trials in other disease areas, including for one FDA approved treatment.

Prevail has exclusive worldwide license agreements with REGENXBIO to develop and commercialize gene therapy products using REGENXBIO’s NAV AAV9 vector to deliver the genes contained in our pipeline programs.


Parkinson's Disease with GBA1 Mutation

We are developing a broad pipeline of gene therapies for a range of neurodegenerative diseases including Parkinson’s disease, frontotemporal dementia, Alzheimer’s disease, and ALS. The first indication for our lead program, PR001, the treatment of Parkinson’s disease with GBA1 mutation (PD-GBA), illustrates our precision medicine approach to treating neurodegenerative disease.

Parkinson’s disease is a chronic, progressive neurodegenerative disorder that affects up to one million people in the United States and more than 7 million people worldwide. While Parkinson’s disease is a movement disorder that is most commonly characterized by resting tremor, bradykinesia, rigidity and gait difficulty, it is now known to impact other aspects of nervous system function, and patients can suffer from a range of non-motor symptoms including psychosis, dementia, and cognitive impairment. Pathologically, Parkinson’s disease is characterized by inclusions called Lewy bodies, which are found within neurons and are comprised predominantly of an aggregated protein called α-Synuclein. There are no treatments available that modify the progressive underlying disease process of Parkinson’s disease.

Gene mapping in recent years has led to the identification of dozens of causative and risk genes for Parkinson’s disease. Many of these genes are involved in lysosomal function or lysosomal trafficking, indicating that lysosome dysfunction is the common denominator that underlies Parkinson’s disease pathology.

For example, mutations in the glucocerebrosidase (GBA1) gene are now known to play an important role in Parkinson’s disease. It is estimated that seven to ten percent of Parkinson’s patients worldwide, and up to 10 percent of Parkinson’s patients in the United States carry a GBA1 mutation. GBA1 encodes the lysosomal enzyme glucocerebrosidase (GCase), which is required for the disposal and recycling of glycolipids, a type of cellular lipid component that is known to accumulate with aging. Reduced levels of GCase activity in Parkinson’s patients with GBA1 mutations may lead to accumulation of glycolipids, which is toxic and can cause inflammation, leading to lysosomal dysfunction and aggregation of α-Synuclein in cells.

We are also developing PR001 for the treatment of neuronopathic Gaucher disease. PD-GBA and Gaucher disease share the same underlying genetic mechanism, as Gaucher disease is defined by the presence of mutations in both chromosomal copies of GBA1, and we believe they represent a continuum of disease.