Chapter 20: Davunetide (NAP) Pharmacology: Neuroprotection and Tau Check Access

Davunetide (generic name for a peptide of eight amino acids, NAPVSIPQ, also known as NAP) is a drug candidate in clinical trials by Allon Therapeutics Inc. (www.allontherapeutics.com). Phase IIa clinical results have shown that davunetide intranasal (AL-108) is safe and well tolerated providing a positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). This chapter describes the discovery of NAP, the active peptide derived from activity-dependent neuroprotective protein (ADNP). The vital roles of ADNP in neuronal development/plasticity are further described. Converging mechanisms including neuroprotection and interaction with the microtubule systems are addressed. The description of the in vivo pharmacology of davunetide (NAP) discloses activity in multiple animal models with highlights on the ADNP-deficient model, the triple transgenic model of Alzheimer's disease and a tau double transgenic mouse model of frontotmporal dementia paving the path to better understanding of neuroprotection and innovative drug discovery and development.