Davunetide (NAP, AL-108) is an eight amino acid peptide derived from the activity-dependent neurotrophic protein (ADNP), a growth factor with diverse neuroprotective activity. [114] In several transgenic mouse models, administration of davunetide increased the amount of microtubule-associated tau and reversed cognitive deficits [115,116]. In a Phase 2 trial in 144 MCI patients, treatment with davunetide for 12 weeks was safe and well-tolerated, but no improvement was seen in pre-specified composite batteries of cognition [117]. However, improvements were seen on individual tests of working memory, tasks known to be profoundly impacted in patients with PSP [118]. These data supported further development in this population, and davunetide entered the first Phase 2/3 trial for PSP, but in 360 patients treated for 52 weeks, no differences were found in primary or secondary outcomes, and development of davunetide was discontined [119].
