Parkinson's disease is caused by the loss of cells in the brain that produce a chemical called dopamine, which is also called a monoamine. The loss of these cells has been delayed in pre-clinical models by the administration of GDNF (glial derived neurotrophic factor), a specialized protein known as a trophic factor which stimulates the dopamine-producing cells. However, this protein does not naturally cross the blood-brain barrier (BBB), meaning it cannot be administered orally (in pill form).
The present work will use a new form of gene therapy, which does not require the use of viruses to deliver the gene, and which can be administered non-invasively by periodic intravenous administration. The new approach uses Trojan horse liposomes to target the GDNF gene across the BBB. A specific "gene switch" will be used to insure the GDNF gene is produced only in the monamine producing cells in brain.
Final Outcome
In the first year of this project, Dr. Pardridge demonstrated a lasting but relatively small therapeutic effect with a single intravenous injection of the non-viral GDNF gene therapy using Trojan horse technology. As a follow-up, Dr. Pardrige demonstrated a lasting and large therapeutic effect with three consecutive weekly injections.
Promising outcomes from this project led to supplemental funding for Dr. Pardridge in 2007 and then a 2008 award to ArmaGen Technologies, Inc., to continue developing this therapeutic approach to GDNF.
Results of the original award were published in the Journal of Genetic Medicine and Pharmaceutical Research.
Researchers
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William M. Pardridge, MD