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Funded Studies

Co-Pathologies Drive Neuroinflammation and Progression in PD

Study Rationale:
While Parkinson’s disease (PD) is considered a synucleinopathy, the clinical progression of PD is driven by additional pathological proteins such as tau and beta-amyloid. Our overarching hypothesis argues that these pathologies, in concert, result in brain inflammation that may be different in character and/or quantity than single pathology states.

Hypothesis:
We will test the hypothesis that the induction of co-pathologies will provide more construct and face validity in the context of human disease, and thus be a superior model for the evaluation of future novel therapies.

Study Design:
Herein we propose to create novel nonhuman primate models of co-pathology and inflammation through treatment with alpha-synuclein preformed fibrils, AAV-tau, and beta-amyloid via aging and transgenesis. We will validate these models by comparing our findings to inflammatory processes seen in human brain samples and refine exploration of the mechanisms involved by blocking these pathologies in mice and nonhuman primates using specific immunotherapies.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
The failure to having discovered disease-modifying treatments for PD may in large part be due to the failure to create relevant animal models to test novel therapeutic strategies. Clearly single pathology models do not reflect the multiple pathologies seen in PD. The mouse and nonhuman primate models to be created and validated in this application along with a deep understanding of their downstream inflammatory pathways will provide essential platforms for testing novel therapeutic strategies.


Researchers

  • Jeffrey H. Kordower, PhD

    Chicago, IL United States


  • Ashley S. Harms, PhD

    Birmingham, AL United States


  • Warren D. Hirst, PhD

    Cambridge, MA United States


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