Microtubules, schizophrenia and cognitive behavior: preclinical development of davunetide (NAP) as a peptide-drug candidate |
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| Authors: | Gozes Illana |
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| Institution: | a The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Adams Super Center for Brain Studies, The Elton Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
b Allon Therapeutics Inc., Vancouver, BC, Canada |
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| Abstract: | NAP (davunetide) is an active fragment of activity-dependent neuroprotective protein (ADNP). ADNP and the homologous protein ADNP2 provide cell protection. ADNP is essential for brain formation, proper development and neuronal plasticity, all reported to be impaired in schizophrenia. ADNP haploinsufficiecy inhibits social and cognitive functions, major hallmarks in schizophrenia. Imbalance in ADNP/ADNP2 expression in the schizophrenia brain may impact disease progression. NAP treatment partly ameliorates ADNP haploinsufficiecy. The microtubule, stable tubule-only polypeptide (STOP)-deficient mice were shown to provide a reliable model for schizophrenia. Daily intranasal NAP treatment significantly decreased hyperactivity in STOP-deficient mice and protected visual memory, supporting further clinical development. |
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| Keywords: | Schizophrenia Stable tubule-only polypeptide (STOP) Tau Activity-dependent neuroprotective protein (ADNP) ADNP2 NAP (davunetide) Hyperactivity Visual memory |
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