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Our Science

We are 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. We are 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. Recent advances in gene therapy technology now allow for the efficient and widespread delivery of gene therapies to the central nervous system.

We are developing adeno-associated virus (AAV)-based gene therapies for the treatment of neurodegenerative diseases. Recombinant AAVs (rAAV) used in our gene therapies 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.


Parkinson's Disease with GBA1 Mutations (PD-GBA)

Parkinson’s disease is a severe and progressive neurodegenerative disorder that affects more than seven million people worldwide and up to one million people in the United States. Although Parkinson’s has historically been characterized as a movement disorder, patients can suffer from a range of non-motor symptoms, including psychosis, dementia and cognitive impairment. Pathologically, Parkinson’s disease is characterized by the presence of abnormal clumps of a protein called α-Synuclein that form in neurons throughout the brain. These protein aggregates are known as Lewy bodies.

There are currently no approved therapies that modify the course of Parkinson’s disease or the underlying pathological process.

Large-scale genetic studies have recently identified dozens of causative and risk genes for Parkinson’s disease. Many of these genes are involved in the normal functioning of lysosomes — so-called “recycling centers” in cells that contain enzymes responsible for degrading proteins, lipids and sugars to regulate metabolic function.

Lysosomal dysfunction plays a role in many types of neurogenerative diseases. In particular, mutations in the GBA1 gene — which helps to regulate lysosomal activity — are now known to be the single largest genetic risk factor for developing Parkinson's disease, causing a subtype of the disorder known as PD-GBA. It is estimated that as many as seven to ten percent of Parkinson’s patients worldwide, and some 90,000 patients in the United States, carry at least one GBA1 mutation. GBA1 encodes the lysosomal enzyme beta-glucocerebrosidase (GCase), which is needed for the disposal and recycling of glycolipids — a type of cellular lipid component that is known to accumulate with aging. Mutations in the GBA1 gene lead to a deficiency of GCase. Without sufficient levels of the enzyme, lysosomes in brain cells cannot do their jobs, and inflammation and neurodegeneration ensue. GBA1 mutations lead to earlier onset of Parkinson’s disease, more severe symptoms, and increased likelihood of progression to dementia.

In addition to Parkinson's disease with GBA1 mutations, we are developing PR001 for the treatment of Type 1 Gaucher disease as well as Type 2 Gaucher disease.

Gaucher Disease

Gaucher disease is a rare genetic disorder driven by mutations in the GBA1 gene, that like PD-GBA, can cause lysosomal dysfunction and have a wide range of effects on organs throughout the body. Gaucher disease and PD-GBA share the same underlying genetic mutation that causes a reduction in the enzyme beta-glucocerebrosidase, or GCase. While PD-GBA is caused by a single GBA1 mutation, Gaucher disease is caused by a mutation in both copies of the GBA1 gene. Diagnosis is suspected by clinical symptoms and confirmed by measuring GBA enzyme activity or genetic testing.

Gaucher disease has three subtypes (Type 1, Type 2 and Type 3), which are classified by variation in the severity of symptoms, age of onset, and the presence or lack of symptoms that affect the brain. Type 1 Gaucher disease (GD1), the most common form, has a wide variety of symptoms, such as spleen and liver enlargement, low blood counts issues with bleeding and bone pain and damage. We have recently initiated our PROCEED trial for patients with Type 1 Gaucher disease (GD1) with the goal of expanding our treatment landscape for a wider range of people living with this disease around the globe.

We are developing PR001 for the treatment of Type 1 Gaucher disease, as well as Parkinson's disease with GBA1 mutations.

Frontotemporal Dementia with GRN Mutations (FTD-GRN)

Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 (after Alzheimer’s disease), affecting 50,000 to 60,000 patients in the U.S. and 80,000 to 110,000 in the European Union. FTD is characterized by the progressive degeneration of the frontal and temporal lobes of the brain, which control decision-making, behavior, emotion and language. Although clinical presentation varies, the disease progresses more rapidly than Alzheimer’s, and death typically occurs three to ten years after the onset of symptoms.

There are currently no approved therapies for FTD.

Several forms of FTD are known to be caused by genetic mutations, which are increasingly well understood. One important example is the GRN gene, which encodes a protein called progranulin that is needed for the normal functioning of lysosomes, microglia, and neurons. Most people carry two normal copies of the GRN gene. Patients with FTD-GRN have mutations in one of their GRN genes that causes them to produce about half as much progranulin as healthy people. This reduction in progranulin lead to age-dependent lysosomal dysfunction, inflammation of the brain, and neurodegeneration.

We are developing PR006 for the treatment of FTD-GRN.

Patients interested in learning more may visit our patients page or email for more information.

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