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Cognitive

Davunetide

Also known as: NAP, AL-108, AL-208, CP201, NAPVSIPQ

Clinical Trials
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Key Facts: Davunetide

Category
Cognitive
FDA Status
Not FDA Approved
Clinical Status
Investigational - Failed phase 2/3 in progressive supranuclear palsy (2012). Earlier programs in MCI, schizophrenia and FTD are inactive. Being redeveloped by ExoNavis Therapeutics for ADNP syndrome (FDA orphan and rare pediatric disease designations) and women with PSP; no registered pivotal trial results. Not approved anywhere.
Banned in Sport (WADA)
Not named on the WADA list, but it has no human therapeutic approval anywhere, so the S0 catch-all (non-approved substances) prohibits it at all times.
Administration
Intranasal spray (an IV form, AL-208, was tested in cardiac surgery)
Typical Dose
30 mg intranasal twice daily (PSP trial dose)
Frequency
Once or twice daily
Duration
12 weeks to 52 weeks in trials
Also Known As
NAP, AL-108, AL-208, CP201, NAPVSIPQ

How does Davunetide work?

NAP comes from ADNP, a protein essential for brain development. In cell and animal studies it interacts with microtubule end-binding proteins (EB1 and EB3), promoting microtubule stability and reducing tau phosphorylation, which is why it was aimed at tauopathies like PSP and Alzheimer's disease. Mutations in the ADNP gene itself cause ADNP syndrome (Helsmoortel-Van der Aa syndrome), and in ADNP-deficient mice NAP improved some behavioral and neural measures, the rationale for that newer program. The PSP trial did not include target-engagement measures, so it never showed the drug was actually doing this in human brains.

What does the research show?

The headline result is negative. In the phase 2/3 PSP trial (Boxer and colleagues, Lancet Neurology 2014), 313 patients got 30 mg intranasal davunetide twice daily or placebo for 52 weeks. Disease progression was identical in both groups on both primary measures (PSP Rating Scale and Schwab and England daily living scale), and the authors concluded davunetide is not an effective treatment for PSP. Earlier phase 2 work was mixed: a 12-week trial in 144 people with amnestic mild cognitive impairment hinted at working-memory benefits, and a schizophrenia trial missed one co-primary endpoint while hitting another. The original developer, Allon Therapeutics, stopped investing and was later absorbed by Paladin Labs. The revival comes from the inventor's group: post hoc reanalyses of the PSP data (Translational Psychiatry 2023, Molecular Psychiatry 2026) report that women declined faster than men and that davunetide slowed decline in women only. A similar sex-split reanalysis of the MCI trial was published in 2024. These findings are interesting but are subgroup analyses of trials that failed overall, done by researchers tied to the company now developing the drug (ExoNavis Therapeutics), so they need a new prospective trial to mean much. ExoNavis has said a phase 3 in children with ADNP syndrome began in 2024, but Alzforum could not find it in trial registries. Davunetide holds FDA orphan and rare pediatric disease designations and EMA orphan status for ADNP syndrome.

Trial Progress:Phase II
Pre
I
II
III
IV
FDA

What doses have been studied?

Human Trials·Large phase 2/3 PSP trial was negative; positive signals come only from post hoc subgroup reanalyses

Typical Dosingⓘ

Community experience

Common Dose

30 mg intranasal twice daily (PSP trial dose)

Range

5-30 mg per intranasal dose in trials

Frequency

Once or twice daily

These are trial doses from studies that mostly failed their main goals. They are not recommendations. No product is approved, and research-chemical NAP has no quality controls behind it.

Research Dosingⓘ

Scientific studies

Clinical trial doses only (investigational, not approved for any use)

Doses from Studies

Duration

12 weeks to 52 weeks in trials

Administration

Intranasal spray (an IV form, AL-208, was tested in cardiac surgery)

When and how is Davunetide taken?

Best Time to Take

Twice daily (trial schedule)

Once or twice daily intranasally in trials

Food Recommendation

With or without food

Why This Timing?

The PSP trial used twice-daily nasal dosing. A 2025 review from the inventor's group discusses circadian effects, but no optimal time of day has been established in humans.

What are the side effects of Davunetide?

Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.

  • ●Nosebleeds (12% vs 8% on placebo in the PSP trial)
  • ●Runny nose (10% vs 5%)
  • ●Nasal discomfort (10% vs under 1%)
  • ●Headache
  • ●Serious adverse events and deaths in the PSP trial were similar to placebo
  • ●No long-term safety data outside trials

References

Research This Peptide Further

Frequently Asked Questions

What does Davunetide do?

Davunetide (NAP) is an eight-amino-acid fragment (NAPVSIPQ) of activity-dependent neuroprotective protein (ADNP), discovered at Tel Aviv University and given as a nasal spray. It was meant to protect brain cells by stabilizing microtubules, the scaffolding that tau normally supports. Its big test, a phase 2/3 trial in progressive supranuclear palsy (PSP), failed cleanly in 2012, and development stalled. It has since been revived by its inventors, who argue it works in women and are pursuing ADNP syndrome, but those claims rest on reanalyses of old data, not a new successful trial.

How does Davunetide work?

NAP comes from ADNP, a protein essential for brain development. In cell and animal studies it interacts with microtubule end-binding proteins (EB1 and EB3), promoting microtubule stability and reducing tau phosphorylation, which is why it was aimed at tauopathies like PSP and Alzheimer's disease. Mutations in the ADNP gene itself cause ADNP syndrome (Helsmoortel-Van der Aa syndrome), and in ADNP-deficient mice NAP improved some behavioral and neural measures, the rationale for that newer program. The PSP trial did not include target-engagement measures, so it never showed the drug was actually doing this in human brains.

Is Davunetide FDA approved?

No, Davunetide is not currently FDA approved. Current status: Investigational - Failed phase 2/3 in progressive supranuclear palsy (2012). Earlier programs in MCI, schizophrenia and FTD are inactive. Being redeveloped by ExoNavis Therapeutics for ADNP syndrome (FDA orphan and rare pediatric disease designations) and women with PSP; no registered pivotal trial results. Not approved anywhere.

Is Davunetide banned in sport?

Not named on the WADA list, but it has no human therapeutic approval anywhere, so the S0 catch-all (non-approved substances) prohibits it at all times.

What are the side effects of Davunetide?

Reported side effects include: Nosebleeds (12% vs 8% on placebo in the PSP trial), Runny nose (10% vs 5%), Nasal discomfort (10% vs under 1%), Headache, Serious adverse events and deaths in the PSP trial were similar to placebo. Individual responses vary based on dosage, duration, and personal health factors.

What is the typical dose of Davunetide?

Community-reported common dose: 30 mg intranasal twice daily (PSP trial dose) (Once or twice daily). Range: 5-30 mg per intranasal dose in trials. Administration: Intranasal spray (an IV form, AL-208, was tested in cardiac surgery). Community-reported doses. Not medical advice. Consult healthcare provider.

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