Article

Davunetide (NAP): the ADNP-derived peptide and its research record

Published 28 October 2026 · CognitivePepti Research Desk

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Prepared by: Research Desk. Sources are linked for verification.

Published 28 October 2026

At a glance

What it is: davunetide, also called NAP, is an eight-amino-acid peptide (NAPVSIPQ) taken from activity-dependent neuroprotective protein (ADNP)
Other names: AL-108 for the intranasal form and AL-208 for an intravenous form, both from Allon Therapeutics; later CP201
Origin: the laboratory of Illana Gozes at Tel Aviv University
Main research thread: microtubules and the protein tau, tested in cell and animal models
Clinical record: a 313-person trial in progressive supranuclear palsy (PSP) did not show efficacy; smaller trials in mild cognitive impairment and schizophrenia were inconclusive
Status: not approved for any use

Where the peptide comes from

ADNP is a protein that regulates gene activity and is needed for normal brain development. Gozes and colleagues identified a short sequence inside it, Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln, and called it NAP after its first three amino acids. In cell studies the fragment interacted with microtubules, the protein tracks that hold neurons in shape and carry cargo along axons.

That link to microtubules is why NAP was studied in models of tauopathy. Tau is a protein that normally stabilises microtubules; in Alzheimer's disease and PSP it becomes over-phosphorylated and forms tangles.

A 2020 study (Ivashko-Pachima et al.) examined how the peptide enters cells and reported uptake by endocytosis.

Animal and fly studies

Tau mouse model (Matsuoka et al., 2008): in mice carrying human tau, three months of intranasal NAP lowered levels of hyperphosphorylated tau, and six months was associated with better scores on cognitive tests
Earlier mouse work (Matsuoka et al., 2007): reported less accumulation of amyloid peptide and tau in a transgenic Alzheimer's mouse model
Fruit flies (Quraishe et al., 2013): NAP was tested in a Drosophila model of tauopathy, a model marked by microtubule loss and disrupted axonal transport

Animal results like these explain why a trial was started. They do not predict what happens in people, and the human trials below tested that directly.

The clinical trials

Progressive supranuclear palsy

The largest trial (Boxer et al., 2014, NCT01110720) randomised 313 people with PSP at 48 centres to intranasal davunetide or placebo for 52 weeks. PSP was chosen because it is a disease driven mainly by tau.

Main outcome: the PSP Rating Scale rose by a median of 11.8 points in both groups, meaning disease progressed equally (p=0.41)
Daily living: the Schwab and England Activities of Daily Living scale also showed no difference (p=0.92)
Safety: there were 54 serious adverse events in each group, and 11 deaths with davunetide against 10 with placebo
Nasal effects: nosebleeds (12% vs 8%), runny nose (10% vs 5%) and nasal discomfort (10% vs under 1%) were more frequent with davunetide

The authors concluded that davunetide did not show efficacy in PSP. Allon Therapeutics funded the trial.

Mild cognitive impairment

A 12-week trial in 144 people with amnestic mild cognitive impairment (Morimoto et al., 2013, NCT00422981) found no significant change in its composite memory score. The same authors reviewed the peptide's development in a 2013 paper.

Schizophrenia

In a 12-week pilot study of 63 people with schizophrenia (Javitt et al., 2012), the MATRICS cognitive battery showed no significant effect (p=.45). A functional measure, the UCSD Performance-based Skills Assessment, showed a nominal difference (p=.048). The peptide was well tolerated, and the authors estimated that 45 to 50 participants per group would be needed for a properly powered trial.

Heart bypass surgery

An intravenous form, AL-208, was tested in people undergoing coronary artery bypass surgery (NCT00404014). A 2025 analysis of that small cohort (Gozes et al.) reported that blood levels of the peptide changed differently over time in men and women, a finding the authors say needs caution.

Later re-analyses by sex

Since 2020 the Gozes group has looked at ADNP in a rare neurodevelopmental condition, ADNP syndrome (Gozes, 2020), and has returned to the earlier trial data with a focus on sex.

MCI trial: a 2024 post hoc analysis (Gozes et al.) split the 2013 results by sex
PSP trial: a 2026 paper in Molecular Psychiatry (Shapira et al.) re-scored the PSP data with the shorter ten-item scale recommended by the US Food and Drug Administration (PSPRS-10) and reported an effect favouring women (P=0.0005). Correlations between spinal fluid tau measures and the score ran in opposite directions in men and women

These are post hoc analyses: the subgroups and the shorter scale were not the trial's pre-set main outcome, and results found this way need a new prospective trial to confirm them. The paper discloses that davunetide is under patent protection, that Gozes is Vice President of Drug Development at ExoNavis Therapeutics and that a co-author consults for the company.

Limitations of the evidence

Negative main trial: the only large trial missed its main outcome and its daily-living measure
Small trials: the MCI and schizophrenia studies were short and underpowered
Post hoc findings: the sex-based results come from re-analysis, not from trials designed to test them
Conflicts of interest: much of the research comes from the inventors' group and companies holding rights to the peptide
Animal-to-human gap: effects on tau in mice did not carry over to measurable clinical change in PSP

Key terms

ADNP: activity-dependent neuroprotective protein, the parent protein of NAP
Tauopathy: a disease in which abnormal tau builds up in brain cells, such as PSP or Alzheimer's disease
PSP Rating Scale (PSPRS): a 28-item clinical scale where higher scores mean more severe disease
Post hoc analysis: an analysis chosen after the data were collected, which can generate hypotheses but not confirm them

Supplier

Purita is a store that sells peptides for laboratory research use only. The link below goes to its neurological research category; check the product page and certificate of analysis for what is actually listed.

Purita neurological category

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