The role of TNF-mediated dopaminergic neurotoxicity in Parkinson's disease: Novel anti-TNF biologics as biochemical tools and new therapeutic agents
The Role of Inflammation in Parkinson's Disease, 2004
This grant builds upon the research from a prior grant:
The research from this grant has continued with the supplementary grant:
In July 2004, at the one-year assessment of our initial grant under the Foundation's Inflammation initiative, we demonstrated that our novel dominant-negative TNFs offered significant in vivo neuroprotection in a chronic model of PD. An important question is whether dominant-negative TNFs could provide equal or similar neuroprotection in other models of PD.
This supplement will allow us to investigate the effectiveness of chronically infused dominant-negative TNFs in the 6-OHDA lesioned pre-clinical model of PD.
Dr. Tansey demonstrated that anti-TNF biologics were protective in animal models of PD. By targeting TNF, these molecules reduce inflammation and protect dopaminergic neurons from neurotoxins. These results validated TNF as a potential therapeutic target for PD. In a follow-up MJFF funded project, Dr. Tansey is investigating developing a gene therapy based approach targeting TNF.
The studies funded by the original Inflammation grant (chronic low dose LPS) and the first supplement (6-OHDA) were published in McCoy et al., 2006 in the Journal of Neuroscience. In addition, these studies served as preliminary data for an NIH R01 application entitled ‘TNF signaling in neurodegeneration’ which was funded in 2006.
Associate Professor of Physiology at Emory University School of Medicine
Location: Atlanta, Georgia, United States