UCSF Gene Therapy Method Allays Parkinson's Symptoms

By Lauren Hammit

Krystof Bankiewicz, MD, PhD

Krystof Bankiewicz, MD, PhD

A novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year.

The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease.

The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years.

“The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.”

Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience.

In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active.

“The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks the substantia nigra, which is a part of the brain that controls movement.

A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.

Related links:

Link to the article in the Journal of Neuroscience:
(Reference: Kells AP et al. “Regeneration of the MPTP-Lesioned Dopaminergic System after Convection-Enhanced Delivery of AAV2-GDNF.” Journal of Neuroscience, Vol. 30 (no. 28), July 14, 2010.)

Link to news release from the National Institute of Neurological Disorders and Stroke:

Link to Dr. Bankiewicz’ Lab: