Davunetide
Also known as: AL-108, AL-208, AL‑108, Allon-108, NAP, NAPVSIPQ
Source Davunetide at Peptiology
Save 10% with code PEPTI-BOSSRABBIT-10
Affiliate link: we earn a commission on purchases made through this link, at no extra cost to you.
Tapping Shop Now & Save 10% copies your 10% off code PEPTI-BOSSRABBIT-10 to your clipboard. Paste it at the Peptiology checkout to claim the discount.
Summary
Davunetide (also called NAP, AL‑108, AL‑208) is an eight‑amino‑acid peptide derived from the activity‑dependent neuroprotective protein (ADNP). It is being investigated as an investigational neuroprotective agent for neurodegenerative conditions such as Alzheimer’s disease, progressive supranuclear palsy, frontotemporal dementia and for cognitive impairment in schizophrenia. The compound is not approved for any indication and is studied primarily via intranasal, intravenous or subcutaneous administration.
Mechanism of Action
Davunetide mimics a short fragment of ADNP and binds to microtubules, promoting their stabilization and protecting them from severing by katanin. It also interferes with glycogen‑synthase‑kinase‑3 (GSK‑3) activity, a key driver of tau hyperphosphorylation, and activates downstream survival pathways including PI‑3K/Akt and MAPK/MEK1. Through these actions it reduces apoptosis, supports axonal transport and mitigates tau‑related pathology.
What the Research Shows
Pre‑clinical work in rodents and dogs demonstrated that davunetide protects neurons from apoptosis, stabilises microtubules and improves behavioural outcomes in models of tauopathy. Ten early‑phase clinical trials reported good tolerability and occasional signals of cognitive benefit in amnestic mild‑cognitive‑impairment and schizophrenia. However, two randomized trials in progressive supranuclear palsy failed to show overall clinical improvement, although a post‑hoc analysis suggested a slowing of disease progression in women. A 2024 double‑blind trial in prodromal Alzheimer’s disease reported sex‑dependent memory effects, with men showing dose‑related gains and women responding at higher doses. Overall, safety data are reassuring, but efficacy results remain mixed and appear to vary by sex and disease stage.
Reported Benefits
Evidence from early trials indicates that davunetide is generally safe and well‑tolerated. Small‑scale studies have reported modest improvements in memory scores for patients with amnestic mild‑cognitive‑impairment and enhanced daily functioning in schizophrenia. Sex‑specific analyses suggest possible slowing of PSP progression in women and dose‑related memory gains in men with prodromal Alzheimer’s disease, highlighting a potential niche for targeted use.
Limitations of the Evidence
Large, adequately powered trials have not consistently demonstrated clinical efficacy; the two PSP studies were negative, and the sex‑specific benefits observed in later analyses are based on post‑hoc subgroup findings. Sample sizes in the Alzheimer’s and schizophrenia investigations were limited, and the mechanisms underlying sex differences remain unclear. As an investigational peptide, davunetide lacks regulatory approval and long‑term outcome data.
Safety Considerations
Pre‑clinical toxicology in rats and dogs at maximum feasible doses showed no major safety concerns. Across ten human trials, davunetide was described as generally safe and well‑tolerated, with no serious adverse events highlighted in the abstracts. Detailed adverse‑event profiles are not provided, so while early data are reassuring, comprehensive safety monitoring remains essential in future studies.
How It Is Administered
Davunetide is formulated as a peptide solution and can be delivered intranasally, intravenously or subcutaneously. Intranasal administration has been emphasized for its favorable brain bioavailability and ease of use in clinical trials.
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
- Progressive supranuclear palsyMovement DisorderModerate
- Alzheimer's diseaseNeurodegenerationModerate
Contraindications
- Hypersensitivity to davunetide or excipientsAllergic/ImmunologicHigh
- Known hypersensitivity to peptide componentsAllergyModerate
Adverse Effects
- Nasal irritationLocal/NasalCommon
- NasopharyngitisInfectiousUncommon
- HeadacheNeurologicUncommonPain in the head or upper neck
- Epistaxis (nosebleed)Local/NasalUncommon
- Transient dizzinessSystemicRare
Drug Interactions
- Tau-targeting therapiesLow
- none identifiedLow
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric populationsAgeRelative
- Pregnant womenReproductiveRelative
- Children <12 yearsAgeRelative
- Severe renal/hepatic impairmentOrgan ImpairmentRelative
Regulatory Status
- European UnionInvestigationalNo EMA marketing authorization.
- United StatesInvestigationalNo FDA approval; studied in clinical trials.
- United KingdomInvestigationalNot licensed for clinical use.
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
- Journal ArticleModerateMorimoto BH, et al.2013-01-01T00:00:00.000000Z
- Journal ArticleModerateKoros C, Stamelou M2016-01-01T00:00:00.000000Z
- Journal ArticleModerateEschlböck S, Krismer F, Wenning GK2016-01-01T00:00:00.000000Z
- Journal ArticleModerateGozes I, Blatt J, Lobyntseva A2024-01-01T00:00:00.000000Z
- Journal ArticleModerateGozes I2011-01-01T00:00:00.000000Z
- Journal ArticleModerateGalushkin A, Gozes I2025-01-01T00:00:00.000000Z
Frequently Asked Questions
What conditions is davunetide being studied for?
Research has focused on Alzheimer’s disease and its prodromal stage, progressive supranuclear palsy, frontotemporal dementia and cognitive impairment associated with schizophrenia, all of which involve microtubule or tau dysfunction.
Has davunetide been approved for any medical use?
No. Davunetide remains an investigational peptide and has not received regulatory approval for any indication. All reported data come from early‑phase clinical trials.
How is davunetide administered in studies?
The peptide has been given as an intranasal spray, as an intravenous infusion, or by subcutaneous injection, with intranasal delivery highlighted for its ability to reach the brain efficiently.
Are there any known side effects?
Published trial abstracts describe davunetide as generally safe and well‑tolerated, and they do not list specific serious adverse events. Detailed safety data have not been disclosed in the available literature.
Why do some studies report benefits only in certain sexes?
Post‑hoc analyses from recent trials suggest that women with progressive supranuclear palsy and men with prodromal Alzheimer’s disease may respond differently, possibly due to sex‑dependent interactions with tau pathways, but these findings need confirmation in larger, prospectively designed studies.
What is Davunetide?
Davunetide (also called NAP, AL‑108, AL‑208) is an eight‑amino‑acid peptide derived from the activity‑dependent neuroprotective protein (ADNP). It is being investigated as an investigational neuroprotective agent for neurodegenerative conditions such as Alzheimer’s disease, progressive supranuclear palsy, frontotemporal dementia and for cognitive impairment in schizophrenia. The compound is not approved for any indication and is studied primarily via intranasal, intravenous or subcutaneous administration.
What is Davunetide used for?
Davunetide is educationally associated with: Tau pathology reduction, Neuroprotection in progressive supranuclear palsy, Cognitive enhancement in schizophrenia, Microtubule stabilization, Cognitive improvement in mild cognitive impairment, Progressive supranuclear palsy, Alzheimer's disease. Educational only — not medical advice.
How is Davunetide administered?
Recorded routes of administration: Intranasal, Intravenous, Subcutaneous.
What are the potential side effects of Davunetide?
Reported adverse effects include: Nasal irritation, Nasopharyngitis, Headache, Epistaxis (nosebleed), Transient dizziness. This list is not exhaustive — consult a qualified clinician.
Who should avoid Davunetide?
Recorded contraindications: Hypersensitivity to davunetide or excipients, Known hypersensitivity to peptide components. Consult a qualified clinician before use.