Small Molecule Activators of the TRK Receptors for Neuroprotection
Final rept. 1 May 2008-30 Apr 2011
VETERANS MEDICAL RESEARCH FOUNDATION (VETERANS AFFAIRS) SAN DIEGO CA
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Our central hypothesis is that asterriquinone activators of the Trk receptors would prevent the neuronal cell death associated with traumatic brain injury and would improve cognitive and motor outcomes. We have developed agonists to TrkA and TrkB. The TrkA agonist has been tested in a preclinical model of cognitive impairment and a model of traumatic brain injury. The drug improves learning in a Morris water maze paradigm and reduces infarct volume in a controlled cortical impact model of brain injury. Preliminary pharmacokinetic data indicates the drug is orally available. Further analogs with improve potency and specificity are being developed.
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