Cognitive & neuro

Davunetide (NAP)

An eight-amino-acid neuroprotective peptide that reached phase 3 trials for a rare brain disease and failed.

Limited evidenceInvestigationalAdd to compare

What it is

Davunetide, also called NAP or AL-108, is an eight-amino-acid peptide (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) derived from activity-dependent neuroprotective protein. It was developed as a nasal spray for neurodegenerative disease and went through a full clinical programme, including a phase 3 trial that did not meet its endpoint.

How it works

1
Binds tubulin and stabilises microtubules, which supports axonal transport.
2
Protects synapses in cell and animal models of neurodegeneration.
3
Reported reduction of tau hyperphosphorylation in models.
4
Reduces amyloid-induced toxicity in cultured neurons.
5
Delivered intranasally in trials to reach the brain directly.

What it's studied for

Mild cognitive impairment (phase 2)

Progressive supranuclear palsy (phase 3)

Cognitive impairment in schizophrenia (phase 2)

Frontotemporal dementia

Reported and studied effects

A small phase 2 trial in mild cognitive impairment reported better memory scores
The phase 3 trial in progressive supranuclear palsy showed no benefit
The schizophrenia cognition trial showed no clear effect
No major safety signal across the programme

Research protocol notes

Research context only

Research context only - an investigational drug that is no longer in development. Trials used intranasal doses of about 5 to 15 mg daily, and up to 30 mg twice daily in the progressive supranuclear palsy study, for 12 to 52 weeks, with cognitive scales or time to dependency as endpoints.

These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.

Possible side effects and contraindications

Safety profile

Possible side effects

Nasal irritation
Headache
No serious safety signal identified in trials
Long-term safety unknown beyond trial durations

Contraindications and cautions

No approved use; it is not available as a medicine
Nasal or sinus disease would limit the delivery route
Pregnancy and childhood - untested

A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.

Evidence assessment

Limited evidenceSmall human studies or animal data only

Small human studies or animal data only

Well-run phase 2 and phase 3 trials exist, but the definitive trial was negative and no regulator has approved it, so the human evidence does not support a benefit claim.

References

References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.

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