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Dr. Greg Gerhardt, Principal Investigator

Restoration of Dopamine Function in Parkinson's Disease
Greg A. Gerhardt
Morris K. Udall Parkinson's Disease Research Center of Excellence at the University of Kentucky Chandler Medical Center

The Udall Center at the University of Kentucky focuses on the use of growth factors to restore function to damaged dopamine neurons in Parkinson's disease (PD). In particular, we focus on the use of nonhuman primate models of PD to lay the foundation for translational search and development of new therapies for the treatment of PD. Our current studies have focused on use of the glial cell line-derived neurotrophic factor (GDNF) to carry out three potential alterations to damaged or dying dopamine neurons: 1) restoration of function of the damaged cells, 2) slow the progression of dying dopamine neurons, and 3) augment the function of remaining dopamine cells. Our studies have involved the development of an infusion delivery system to directly deliver GDNF to the brain of animal models of PD. In addition, our work has resulted in the development of a Phase I clinical trial on the use of GDNF in patients with advanced PD. Our major milestones over the last year are as follows:

1. Development of a mild but stable human primate model of PD that may simulate the earlier stages of PD. We feel that neurotrophic factors may be most effective in the earlier stages of PD, and this animal model has been developed to investigate this hypothesis.
2. Studies have been carried out with direct delivery of GDNF into the substantia nigra of nonhuman primates made parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These studies have demonstrated that focal delivery of GDNF into the substantia nigra is effective for altering the function of remaining dopamine neurons in these animal models of PD.
3. Functional magnetic resonance imaging (fMRI) studies in awake monkeys treated with MPTP to investigate the effects of GDNF treatment on basal ganglia circuitry. These studies have shown interesting changes in the functional properties of the basal ganglia as assessed using fMRI blood oxygen level dependent (BOLD) methods in awake rhesus monkeys, which have been made parkinsonian with MPTP and treatment with GDNF.
4. Phase I clinical trial on the use of GDNF in patients with advanced PD. While the PD funding from the Udall Center award was not used for this trial, the basic science studies laid the foundation for a Phase I clinical trial in patients with advanced PD that were supported by Amgen, Inc., and Medtronic, Inc. The results are in press and will appear in February 2005 in the Journal of Neurosurgery (see Slevin et al., 2005).

Contact Information or Udall Center Link:
University of Kentucky Udall Center of Excellence

Last updated August 13, 2008