Active research is being done in the application of gene transfer to study animal models of neurodegenerative disorders including Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, brain tumors, and ischemia.
Two different strategies will be investigated to alleviate behavioral deficits in rat models of Parkinson’s disease (PD). Both direct intrastriatal transmitter replacement (L-dopa delivery) and neurotrophic support strategies (GDNF delivery) in the unilateral 6-OHDA lesion model of PD using recombinant adeno-associated viral vectors (rAAV) are being pusrued. There is a plan to begin analogous studies in primates to obtain the data necessary to support a Phase I clinical trial using rAAV in PD. This field has been greatly engergized lately by very positive findings reported from Jeffrey Kordower’s laboratory using a recombinant lentivirus to deliver GDNF to the rhesus monkey striatum. Very important studies are underway to develop regulated vectors to express GDNF.
The laboratory will begin experiments using rAAV to transfer ribozymes to the striatum of transgenic mice expressing a mutant form of huntingtin to determine if knocking down gene expression will block Huntington’s disease-like pathology. Other potential projects involving gene transfer in Huntington’s disease models concern the trophic factors brain derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF).