Davunetide

Summary

Davunetide (NAP, AL-108/AL-208) is a short neuroprotective peptide derived from the ADNP protein. It has demonstrated preclinical efficacy in models of Alzheimer's disease, schizophrenia, and other neurodegenerative conditions by stabilizing microtubules and reducing tau pathology. Clinical development included trials in mild cognitive impairment, schizophrenia, and progressive supranuclear palsy (PSP), but Phase 2/3 trials in PSP failed to meet primary endpoints, halting further clinical development.

Mechanism of Action

Davunetide (NAP) is an 8-amino acid peptide derived from activity-dependent neuroprotective protein (ADNP). It interacts with microtubule-associated proteins and tubulin, stabilizing microtubule dynamics, reducing tau hyperphosphorylation, and protecting neurons against oxidative stress and excitotoxicity.

Routes of Administration

Goals & Uses

• Tau pathology reductionNeurodegenerative DiseaseModerate
• Neuroprotection in progressive supranuclear palsyNeurodegenerative DiseaseLow
• Cognitive enhancement in schizophreniaPsychiatric DisorderLow
• Microtubule stabilizationMechanism Based TargetModerate
• Cognitive improvement in mild cognitive impairmentCognitive EnhancementLow

Contraindications

• Hypersensitivity to davunetide or excipientsAllergic/ImmunologicHigh

Adverse Effects

• Nasal irritationLocal/NasalCommon
• NasopharyngitisInfectiousUncommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• Epistaxis (nosebleed)Local/NasalUncommon

Drug Interactions

• Tau-targeting therapiesLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric populationsAgeRelative
• Severe renal/hepatic impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalClinical trials conducted in EU as part of international PSP trial program; no marketing authorization sought or granted.
• United StatesInvestigationalInvestigated under IND for PSP, MCI, and schizophrenia. Development halted after Phase 2/3 PSP trial failure in 2013. No current active development known.
• United KingdomUnknownNo known regulatory submissions or approvals in the UK.

Not approved in any jurisdiction. Development was halted after the Phase 2/3 DAVUNETIDE trial in progressive supranuclear palsy did not meet its primary endpoint (2013). No active IND or regulatory filing known to be ongoing.

Evidence & Sources

No sources recorded yet.