Parkinson's Disease

Experimental Therapies

Cell Transplant Therapy
Transplant of fetal substantia nigra cells has been performed in several hundred patients to date in multiple centers throughout the world. While results have been encouraging in some individual patients, two double-blind placebo-controlled studies showed that consistent benefit was only seen in younger PD patients (age 60 or below), and side effects in some patients were significant. In particular, some patients developed off-medication dyskinesias even without any levodopa or other dopaminergic medication. The lack of consistently good results and the significant side effects encountered have been interpreted by the scientific and medical community to indicate that further research in animal models of PD is needed to improve upon what has been observed to date before more studies in PD patients are undertaken.

Another cell transplant technique that shows some promise is the use of retinal pigment epithelial cells. These cells are derived from tissue at the back of the eye, and they produce and release dopamine. An open-label trial in six advanced PD patients has shown promise, and as of mid-2004, a double-blind trial is underway.

Gene Therapy
As of 2007, gene therapy has been tried in only a few PD patients. The only publicized trial is of delivery of the gene for glutamic acid decarboxylase (GAD) to the STN. GAD is a key enzyme in the production of the inhibitory neurotransmitter GABA. Gene therapy with GAD is meant to increase GABA production, reducing subthalamic nucleus (STN) activity in the manner of STN DBS. A very small phase I trial indicates that 12 months of treatment appears to be safe, and may improve motor symptoms.

• MG Kaplitt, A Feigin, C Tang, HL Fitzsimmons, P Mattis, PA Lawlor, RJ Bland, D Young, K Strybing, D Eidelberg, MJ During. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: An open-label, phase I trial. Lancet 2007;369:2097-2105

Growth Factor Delivery
Glial cell-derived neurotrophic factor (GDNF) stimulates sprouting of dopaminergic neurons in animal models. Delivery of GDNF to the ventricles in PD patients has proven unsuccessful, possibly because GDNF cannot migrate far enough to reach the nigral cells. Direct delivery of GDNF to the striatum has produced promising results in an open trial in a small number of patients; however, a larger, double-blind trial failed to show efficacy, and the manufacturer withdrew GDNF from trials over concerns for safety.