IND-Enabling Studies on AAV2-GDNF for Parkinson’s Disease

Parkinson’s disease is a progressive disorder of the nervous system in which brain cells gradually deteriorate and die, causing a decrease in dopamine in the brain. This leads to abnormal brain activity and symptoms of disease. Scientists do not fully understand the causes of Parkinson’s, but it may have both genetic and environmental components. Progression of Parkinson’s varies from person to person, but in its later stages, a person may require nearly total care. As many as 1 million Americans live with the disease, and about 60,000 new cases are diagnosed each year. Men are at higher risk for Parkinson’s than women, and risk increases with age. Currently there is no cure, although medications are available to help control many of the symptoms. These researchers are developing a gene therapy for Parkinson’s that will act by helping to reduce the loss of key, dopamine-producing brain cells.

Scientific Synopsis

The overall aim of this program is to acquire all of the outstanding preclinical data required for submission of an Investigational New Drug (IND) application for the development of AAV2-GDNF as a treatment for Parkinson’s disease (PD). Over the last decade, it has become clear that glia-derived growth factor (GDNF) exhibits remarkably potent trophic effects upon dopaminergic neurons of the substantia nigra. Loss of these key neurons underlies many of the movement and psychological deficits in the disease. A major technical challenge to GDNF therapy has been the development of a means to deliver this small protein into the brain in a focused and predictable manner. On this basis, we have been developing a gene therapy approach to solving this problem. Pre-IND discussions with the FDA have defined a series of preclinical studies that must be completed before we are in a position to file an IND.

We are near completion of two major safety and efficacy studies in non-human primates. These studies incorporate analyses and end-points suggested by the FDA and include determinations of organ pathology, including neuropathology, specifically addressed in this proposal. In addition, qualification of GMP vector to be manufactured at Children’s Hospital of Philadelphia (CHOP) requires that a GLP toxicity study in rats be commissioned, and this also includes extensive organ pathology and biodistribution.

Specifically, therefore, we propose that the following activities be supported under the program in support of our IND-enabling studies:

  • GMP manufacture of AAV2-GDNF at CHOP
  • GLP toxicity study in normal rats
  • Biodistribution study
  • Neuropathological assessments of rodent and NHP brain

These studies, along with supporting data accrued at UCSF, would enable compilation of an IND. If accepted by the FDA, we would be in a position to undertake a well-designed, NIH-supported clinical study of the safety and efficacy of AAV2-GDNF gene therapy for Parkinson’s disease.

Lead Collaborator

University of California, San Francisco
Krzysztof Bankiewicz, M.D., Ph.D.

Public Health Impact

Translation of AAV2-GDNF gene therapy into clinical study is likely to improve prospects for significant reversal of the symptoms of Parkinson’s disease.


Work on this project is complete. The investigators successfully filed an IND application using BrIDGs data and initiated clinical testing.

Project Details

  • Investigational New Drug (IND)-directed toxicology