ABS 205, a small organic compound that penetrates the brain and enhances cognitive ability in animal models of compromised learning has been identified as the lead in a series of related compounds. ABS 205 exhibits neurotrophic-like activity in-vitro, similar to the effects of nerve growth factor (NGF), by enhancing cell survival and promoting neuritogenesis. Like NGF, ABS 205 enhances expression of the neural cell adhesion molecule (NCAM) and causes its posttranslational modification (polysialylation). NCAM polysialylation is modulated through protein kinease C (PKC) expression. Polysialylated NCAM is important in neurodevelopment and memory processing, and exhibits age-dependent decline, consistent with loss of cognitive function. This application proposes to: extend previous cognitive studies by examining the effects of acute and chronic administration of ABS 205 on cognition in a spatial learning paradigm; evaluate the effects on age-associated decline in NCAM polysialylation in-vivo; and elucidate the mechanism by which ABS 205 modulates NCAM expression by examining its influence on PKC in-vitro. The proposed work will help American Biogenetic Sciences, Inc. evaluate ABS 205 as a treatment for cognitive dysfunction associated with aging and Alzheimer's disease. In addition, the in-vitro PKC assay may provide a novel mechanism of screening for chemically distinct neurotrophic agents. PROPOSED COMMERCIAL APPLICATION: ABS 205 is a small organic molecule which can cross into brain tissue. This compound has neurotropic-like activity similar to NGF with cognition- enhancing abilities. ABS 205 has potential for treatment of cognitive dysfunction associated with aging, Alzheimer's disease and other neurodegerative disorders. There is a huge unmet commercial need for agents which can effectively treat these disorders.
Thesaurus Terms: Alzheimer's disease, drug screening /evaluation, neural degeneration, neuropharmacology, neurotrophic factor N acylation, cognition, enzyme activity, isozyme, neural cell adhesion molecule, protein kinase C immunocytochemistry, laboratory rat, neuron, neuropsychological test, tissue /cell culture
