Davunetide (NAP / AL-108)
Eight-amino-acid neuroprotective peptide derived from activity-dependent neuroprotective protein (ADNP).
At a glance
What it is: Eight-amino-acid neuroprotective peptide derived from activity-dependent neuroprotective protein (ADNP)..
Primary research applications:
- Neurodegenerative disease research
- Tauopathy and progressive supranuclear palsy (PSP) — earlier trials
- ADNP syndrome research
Editorial summary: Davunetide is the most clinically advanced product derived from the activity-dependent neuroprotective protein (ADNP) family. Its neuroprotective biology is well characterized in basic science, but Phase 3 trials in tauopathies (notably progressive supranuclear palsy) did not meet primary endpoints. The molecule remains an active research probe for ADNP-related neurodevelopmental disease and broader neuroprotection concepts.
- Class / structure
- Eight-amino-acid peptide (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) derived from ADNP
- Half-life
- Short systemic; intranasal delivery used in trials
- First described
- 1990s (Illana Gozes group, Tel Aviv University)
- Regulatory status
- Investigational; Phase 2 active in selected indications
What is Davunetide?
Davunetide (also called NAP or AL-108 in earlier development) is a synthetic eight-amino-acid peptide retaining the active region of the ADNP protein.
Discovery and development
Davunetide is the synthetic eight-amino-acid active fragment of activity-dependent neuroprotective protein (ADNP), a master regulator of brain development discovered by Illana Gozes and colleagues at Tel Aviv University. The peptide retains ADNP's neuroprotective activity in a form suitable for therapeutic delivery, particularly intranasally.
Mechanism of action
The peptide acts on multiple neuroprotective pathways:
- Microtubule stabilization via interaction with end-binding proteins (EB1, EB3).
- Reduction of tau hyperphosphorylation in tauopathy models.
- Anti-apoptotic and anti-oxidative effects in neurons.
The microtubule-stabilizing mechanism distinguishes it from most other neuroprotective peptide concepts.[1]
Pharmacokinetics
Davunetide has been delivered intranasally in most clinical research, taking advantage of olfactory and trigeminal pathways to reach the central nervous system. Plasma half-life is short; tissue effects extend beyond plasma clearance.
What the research shows
The peer-reviewed literature on Davunetide is summarized below across two tiers: human research (the highest standard), and preclinical / emerging research (animal models and early-stage human work).
Claims and the evidence behind them
This table summarizes commonly discussed claims and how the published evidence weighs in. The aim is clarity — supported claims, claims that look promising but need more data, and claims that outrun the science.
| Claim | What the evidence shows | Verdict |
|---|---|---|
| Has neuroprotective activity in animal models | Extensive preclinical literature | Supported |
| Improves clinical outcomes in PSP | Phase 3 did not meet primary endpoints | Unsupported |
| Should be used as a general cognitive enhancer | Not supported by trial evidence | Unsupported |
Reported user experiences
How the research describes administration
Most published research has used intranasal administration. The molecule is not commercially available outside trial enrollment.
Editorial note
Administration details above describe how the peptide is given in published studies. We summarize this for educational completeness — these descriptions are not protocols, dosing recommendations, or instructions for personal use. Decisions about treatment require an appropriately licensed clinician.
Safety considerations and open questions
The takeaway
Davunetide is one of the more rigorously studied neuroprotective peptides, with a clear molecular mechanism (microtubule stabilization via EB protein interactions) and a well-defined development arc that includes both informative successes in basic science and instructive setbacks in late-stage clinical trials. It remains a serious research compound rather than a settled clinical tool.
Frequently asked questions
Is davunetide approved for any indication?
No. As of 2026 it is investigational, with active research particularly in ADNP syndrome and other tauopathy-related contexts.
How does davunetide differ from cerebrolysin?
Cerebrolysin is a porcine-brain-derived peptide-amino-acid mixture; davunetide is a single defined eight-amino-acid synthetic peptide with a specific microtubule-stabilization mechanism. Different molecular and clinical profiles entirely.
References
- Gozes I, et al. NAP (davunetide) provides functional and structural neuroprotection. Curr Pharm Des. 2011;17(10):1040-1044. https://pubmed.ncbi.nlm.nih.gov/21524259/
- Boxer AL, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014;13(7):676-685. https://pubmed.ncbi.nlm.nih.gov/24873720/