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Transcript
The use of Pan-PPAR Agonists for Treatment of Tauopathies and Huntington’s disease Inventor: Flint Beal, MD Chairman of Neurology and Neuroscience/Neurologist-in-Chief New York Presbyterian Hospital-Weill Medical College of Cornell University PPAR and neuroprotection • Well established field – 92 hits on pubmed; 13 reviews • Great review of pan-PPAR agonism by Beal, 2008 • PPAR agonists are anti-inflammatory, antioxidant, protect mitochondria “Modulation of several molecular and pathophysiological pathways simultaneously may be a better approach for neuroprotection. This could be achieved by using a combination of several pharmacological agents or, preferably, with only one having pleiotrophic effects. PPAR agonists have the ability to induce gene expression and modulate several molecular pathways at the level of transcription. Therefore, PPAR agonists or drugs acting on transcription factor receptors are possible therapeutic targets for neurodegenerative diseases. Further, additional experimental, preclinical and clinical studies are necessary using PPAR agonists to determine neuroprotective effects on disease progression as well as on disease onset.’ What’s new? • Reduction to practice in P301S mice (tauopathy) • Reduction to practice in HD mouse Bezafibrate reduced tau pathology in P301S mice. Bezafibrate rescued behavioral abnormalities in P301S mice Bezafibrate restores the PGC-1α signaling pathway in R6/2 mice Bezafibrate improves the behavioral phenotype and extends survival in R6/2 mice • Developmental status – POC established in 2 mouse models with bezafibrate • Intellectual Property – Provisional application filed • Publications – Johri A et al. (2012) Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington's disease. Hum Mol Genet. 2012 Mar 1;21(5):1124-37. Contact: Bruce Toman, CLP Technology Commercialization and Liaison Officer CCTEC 418 E 71st Street, Suite 61 New York, NY 10021 ph: 212-746-6187 [email protected]
