Novel Gene Therapy Treatment for Parkinson’s Disease Shows Promise

It is estimated that 60,000 new cases of Parkinson’s disease (PD) are diagnosed each year, adding to the estimated one to 1.5 million Americans who currently have the disease. The latest epidemiology studies indicate that worldwide numbers will increase from an estimated 4.1 million in 2005 to 8.7 million people with PD by 2030. There were nearly 18,000 PD-related deaths in the United States in 2004. While the condition usually develops after the age of 55, the disease may affect people in their 30s and 40s.

Early in the disease, there is a loss of brain cells that produce the chemical dopamine. Normally, dopamine operates in a delicate balance with other neurotransmitters to help coordinate the millions of nerve and muscle cells involved in movement. Without enough dopamine, this balance is disrupted, resulting in tremor (trembling in the hands, arms, legs and jaw); rigidity (stiffness of the limbs); slowness of movement; and impaired balance and coordination – the hallmark symptoms of PD.

In the last 10 years, protein substances called “growth factors” have been discovered that can slow or halt the death of dopamine-producing cells. One such factor, known as “GDNF” (Glia-Derived Neurotrophic Factor), has been used in clinical trials for PD. The results have been inconsistent, possibly related to the method of delivering the protein to the brain.

Researchers at the University of California at San Francisco, and Rush-Presbyterian Medical Center in Chicago, in conjunction with Ceregene, Inc. of San Diego, Calif., recently undertook a Phase I trial using a novel strategy called “gene transfer” to deliver a growth factor to the brains of 12 patients with PD. All patients entered in the trial were judged to have inadequate control of their disease with standard levadopa therapy and would have otherwise been potential candidates for treatment interventions such as deep brain stimulation (DBS).

The results of this study, Intrastriatal Gene Transfer with AAV-Neurturin for Parkinson’s Disease: Results of a Phase I Trial, will be presented by Philip A. Starr, MD, PhD, 11:45 am to 12:00 p.m. on Monday, April 16, 2007, during the 75th Annual Meeting of the American Association of Neurological Surgeons in Washington, D.C. Co-authors are Leo Verhagen, MD, Paul S. Larson, MD, Roy Bakay, MD, Robin Taylor, RN, Deborah Cahn-Weiner, PhD, Raymond Bartus, MD, Jill L. Ostrem, MD, and William J. Marks Jr., MD.

The growth factor gene was delivered as part of a modified virus, or “viral vector”, called adeno-associated virus (AAV). This viral vector helps enable the gene to be delivered into the correct brain cells, but has been modified so that it cannot reproduce or damage brain cells. The growth factor gene neurturin was utilized, which is a protein closely related to GDNF. Neurturin has been shown in laboratory studies to help prolong survival of dopamine-making cells. AAV-neurturin was delivered directly to the brain via stereotactic injection through multiple (16) needle injections into the striatum, the part of the brain most deficient in dopamine. This was performed through small openings in the skull.