Barbara L. Waszczak
Department of Pharmaceutical Sciences, Faculty, School of Pharmacy
Office: 140 TF, Room 269
Professor of Pharmacology, Pharmaceutical Sciences
The Waszczak laboratory at Northeastern University is focused on developing an intranasal therapy for Parkinson’s disease (PD) using glial cell line-derived neurotrophic factor (GDNF), or DNA nanoparticles (NPs) encoding GDNF. GDNF is an endogenously-expressed trophic factor for the dopaminergic neurons which die in PD. If given early in the disease, it is widely believed that GDNF could arrest PD progression and promote the recovery and regeneration of the surviving dopamine neurons. The main obstacle is getting GDNF into the brain by a non-invasive route of administration. A number of clinical trials have already been undertaken using brain infusions of GDNF, or viral vectors encoding GDNF, but most PD patients would not be eligible for such a surgical approach. A much larger proportion of early- to mid-stage PD patients could benefit from a non-immunogenic GDNF therapy given by a non-invasive route of administration. To that end, we have demonstrated that intranasal administration of GDNF protein, and GDNF DNA NPs, bypass the blood-brain barrier (BBB) and provide significant protection of dopaminergic neurons in the rat 6-hydroxydopmaine model of PD. DNA NPs encoding GDNF are an especially appealing approach because they transfect cells in brain, thereby generating a renewable source of GDNF within the brain. Although our focus is on a GDNF therapy for PD, there is tremendous potential for intranasal administration of DNA NPs encoding other trophic factors to be therapeutic in a host of CNS neurodegenerative disorders. The Waszczak lab is working in collaboration with Copernicus Therapeutics, a small biotechnology company in Cleveland, which has optimized a GDNF expression plasmid and formulated the DNA NPs. Northeastern University and Copernicus jointly filed a patent application on this approach and are actively seeking industry partners to commercialize and market intranasal gene therapies for brain neurodegenerative disorders.
Migliore, M.M., T.K. Vyas, R.B. Campbell, M.M. Amiji and B.L. Waszczak, Brain delivery of proteins by the intranasal route of administration: A comparison of cationic liposomes versus aqueous solution formulations. J. Pharm. Sci. 99: 1745-1761, 2010.
Migliore, M.M., R. Ortiz, S. Dye, R.B. Campbell, M.M. Amiji and B.L. Waszczak, Neurotrophic and neuroprotective efficacy of intranasal GDNF in a rat model of Parkinson’s disease. Neuroscience 274: 11-23, 2014.
Harmon, B.T., A.E. Aly, L. Padegimas, O. Sesenoglu-Laird, M.J. Cooper and B.L. Waszczak, Intranasal administration of plasmid DNA nanoparticles yields successful transfection and expression of a reporter protein in rat brain. Gene Therapy 21: 514-521, 2014.