Characterization of a Regulated Recombinant Adeno-Associated Viral Vector Encoding Human GDNF for the Treatment of Parkinson’s Disease

Mandel, Ronald J., Ph.D.
University of Florida College of Medicine, Gainesville, Fl


Dr. Ronald J. Mandel will use recombinant adeno-associated viral vector (rAAV) methods to inject GDNF(glial cell-derived neurotrophic factor) into rat striata and then treat half the animals with oral antibiotic to determine if these animals are thus protected against drug-induced parkinsonism (by comparison with the other half or control group). He and his colleagues at the University of Florida are trying to devise a non-invasive delivery method of administering a trophic factor that they and others have shown to positively affect DA neurons.The use of rAAV vectors is safe in that the viral genes have been removed.Gene transfer could become such a method of delivery and be useful in various neurodegenerative disorders.

Progress Report (as of 8/2002)

Numerous groups have now used recombinant adeno-associated viruses (rAAV) to add glial-derived neurotrophic factor (GDNF) to relieve the disorder in the brains of animals made parkinsonian, usually by MPTP injections. The problem before taking this therapy to human trials is that control of the amount of GDNF and the distances to which it is transmitted has yet to be determined. Dr. Ronald J. Mandel and his group at the University of South Florida used the antibiotic tetracycline to regulate transgene expression in parkinsonian rats, the element used consisting of a transactivator (the starter) and a silencer (the stopper).