reviewed april 2026|next review october 2026|88 physicians psi has verified|13116 published studies
Davunetide (NAP/AL-108)
Davunetide (NAP, AL-108) is an 8-amino-acid neuroprotective peptide derived from activity-dependent neuroprotective protein (ADNP) that stabilizes microtubules through a mechanism distinct from taxol-class drugs, with Phase II/III trial failure in progressive supranuclear palsy.
Evidence landscape: 13116 published studies
13,116 published items (inflated by broad neuroprotection query). 8 human studies and 151 animal studies.
- 8 Human
- 151 Animal
- 41 Reviews
- 12916 Other research
Not FDA-approved. Clinical development was discontinued after the Phase II/III trial in progressive supranuclear palsy (PSP) failed its primary endpoints. No active clinical development program.
Clinical development discontinued. Not available as a pharmaceutical. Available as a research compound from some peptide suppliers.
Neuroprotective peptide with a unique microtubule-stabilizing mechanism distinct from taxol-class drugs. Derived from ADNP (activity-dependent neuroprotective protein), one of the most abundant neuroprotective proteins in the brain. Intranasal delivery demonstrated in clinical trials.
PSI Assessment
A neuroprotective peptide derived from activity-dependent neuroprotective protein (ADNP) that produced compelling animal data for neurodegeneration, davunetide (also called NAP or AL-108) advanced to Phase II/III clinical trials for progressive supranuclear palsy (PSP, a rare tauopathy) and failed its primary endpoints. The failure was notable because the animal signal for tau-related neuroprotection was strong: davunetide stabilizes microtubules (the structural scaffolding inside neurons) through a mechanism distinct from taxol-class drugs. The PSP trial failure did not disprove the mechanism but raised questions about whether the target population, disease stage, or dosing were appropriate.
Strong animal neuroprotection data. Phase II/III PSP trial failed its primary endpoints. The mechanism remains valid; the clinical translation did not succeed.
The mechanism is microtubule stabilization through direct tubulin binding. The 8-amino-acid sequence (NAPVSIPQ) is derived from ADNP, one of the most abundant neuroprotective proteins in the brain. In tauopathies like PSP, tau protein dysfunction leads to microtubule collapse, which disrupts axonal transport and causes neuronal death. Davunetide was designed to compensate for this loss of microtubule stability. Intranasal delivery provides direct CNS access.
What the evidence supports
Davunetide stabilizes microtubules through direct tubulin binding, a mechanism distinct from taxol-class drugs. Animal models of neurodegeneration consistently show neuroprotective effects. Intranasal bioavailability provides a practical delivery route. The ADNP-derived mechanism is pharmacologically characterized.
What is not yet established
Whether davunetide can produce neuroprotection in human neurodegenerative disease. The Phase II/III trial in progressive supranuclear palsy failed its primary endpoints. Whether the failure reflects the wrong disease target, wrong dosing, wrong patient population, or a fundamental limitation of the approach. The development program was discontinued after the PSP trial failure.
Research Evidence
The findings below cover the animal and laboratory mechanism, the clinical trial failure, and the remaining open questions.
Evidence by condition
Evidence dimensions across davunetide research areas. Neurodegeneration/tauopathies have Phase II/III trial data (failed endpoints). Cognitive protection has exploratory human data from schizophrenia. Microtubule stabilization has extensive animal and laboratory characterization.
| Condition | Mechanism | Animal evidence | Human evidence | Replication |
|---|---|---|---|---|
| Neurodegeneration/Tauopathies | ||||
| Cognitive Protection | ||||
| Microtubule Stabilization |
Davunetide stabilizes microtubules through direct tubulin binding, providing neuroprotection across multiple animal models of neurodegeneration including tau-mediated neuronal death. The mechanism is distinct from taxol-class microtubule stabilizers.
The animal and laboratory neuroprotection data was consistently positive across multiple models and research groups, which supported advancement to clinical trials.
The Phase II/III randomized controlled trial of intranasal davunetide in 313 patients with progressive supranuclear palsy did not meet its primary endpoint (PSPRS score change) or key secondary endpoints. The trial demonstrated safety and tolerability but not efficacy.
PSP is a rare and aggressive tauopathy. Whether the failure reflects the wrong disease target, insufficient dose, too-advanced disease stage, or a fundamental limitation of microtubule stabilization for neurodegeneration remains debated.
Intranasal davunetide improved cognitive function in a clinical study of patients with schizophrenia. This cognitive signal in a different patient population suggests the mechanism may have applications beyond tauopathies.
The schizophrenia cognitive data is from an exploratory study and does not compensate for the PSP trial failure. It does suggest that the compound reaches the brain and produces measurable effects on cognition.
8 Human|151 Animal|41 Reviews
View all 13116 indexed studiesHow Davunetide (NAP/AL-108) Works
Davunetide is an 8-amino-acid peptide, one of the shortest neuroprotective peptides studied in clinical trials. Its sequence (NAPVSIPQ) comes from ADNP (activity-dependent neuroprotective protein), a protein the brain naturally produces in large quantities to protect neurons. Davunetide was designed to deliver the active neuroprotective fragment of ADNP directly to the brain via intranasal (through the nose) administration.
Neurons contain a highway system of tiny tubes (microtubules) that transport essential cargo. In neurodegenerative diseases, these tubes fall apart. Davunetide stabilizes the tubes, keeping neuronal highways intact for transport.
For a more detailed view of the biology, here is what researchers have observed at the molecular level.
NAPVSIPQ octapeptide derived from activity-dependent neuroprotective protein (ADNP). Binds tubulin and promotes microtubule assembly and stability through a mechanism distinct from taxol-class stabilizers. Protects against tau-mediated microtubule dysfunction by compensating for the loss of tau's normal microtubule-stabilizing function. Reduces tau hyperphosphorylation and protects against oxidative stress, excitotoxicity, and amyloid-beta toxicity in animal and laboratory models. Intranasal delivery bypasses the blood-brain barrier.
What is Davunetide (NAP/AL-108) being studied for?
Researchers are studying Davunetide (NAP/AL-108) across several health conditions. Each condition below is labeled with the strength of evidence that exists for that specific use, not for Davunetide (NAP/AL-108) overall. This means a compound can have human studies for one condition but only animal data for another.
Neurodegeneration/Tauopathies
·Human TrialsPhase II/III trial in progressive supranuclear palsy demonstrated safety but failed primary efficacy endpoints. Animal models consistently show neuroprotection against tau-mediated neuronal death.
Limitations: The PSP trial failure is the defining result. Development was discontinued. Whether a different target population, dosing, or disease stage would yield different results is unknown.
Cognitive Protection
·Animal StudiesIntranasal davunetide improved cognitive function in an exploratory study of patients with schizophrenia.
Limitations: Exploratory study, not a pivotal trial. Cognitive improvement in schizophrenia does not directly translate to neurodegeneration applications.
Microtubule Stabilization
·Animal StudiesThe microtubule-stabilizing mechanism is well-characterized preclinically with direct tubulin binding demonstrated across multiple studies.
Limitations: The mechanism is validated in vitro and in animal models. Whether pharmacological microtubule stabilization can prevent or slow neurodegeneration in humans remains unproven.
Safety and Regulatory Status
FDA Status: Not FDA-approved. Phase II/III trial completed; development discontinued after failure to meet primary endpoints. No active clinical development.
Availability: Clinical development discontinued. Not available as a pharmaceutical. Available as a research compound from some peptide suppliers.
Class context: Well-tolerated in clinical trials. Intranasal administration showed a favorable safety profile in the PSP trial (313 patients). The trial failed on efficacy, not safety. No significant safety concerns were identified during clinical development.
Davunetide was well-tolerated in clinical trials involving over 300 patients. The Phase II/III PSP trial failed its efficacy endpoints, not its safety endpoints. Intranasal administration was practical and well-accepted. No significant adverse effects were identified during clinical development.
Peptide Structure
Technical molecular data for researchers and clinicians.
Questions and Comparisons
Questions the evidence raises for a Davunetide (NAP/AL-108) discussion.
Comparison and Related Research
Davunetide is most often compared with other neuroprotective compounds, particularly those targeting neurodegeneration.
Related compounds
Frequently Asked Questions
References
Each citation links to the original study on PubMed, the U.S. National Library of Medicine database.
- 1.The definitive Phase II/III trial testing davunetide in progressive supranuclear palsy (PSP). Despite strong preclinical rationale, the trial did not meet its primary or secondary endpoints. This negative result was significant because it was one of the first large-scale randomized trials in PSP, and the failure shifted research focus in the tauopathy field.Boxer AL et al., 2014 in Lancet Neurol. View on PubMed
- 2.Foundational review describing the development of NAP (davunetide) from its parent protein ADNP (activity-dependent neuroprotective protein). Summarized preclinical evidence showing neuroprotective effects across multiple models of neurodegeneration, including protection against oxidative stress and tau-related pathology.Gozes I, 2005 in CNS Drug Rev. View on PubMed
- 3.Phase II trial evaluating intranasal davunetide (AL-108) in patients with schizophrenia. The study assessed cognitive endpoints and functional capacity measures, contributing to the clinical dataset for this neuroprotective peptide outside of its primary neurodegenerative disease indications.Javitt DC et al., 2012 in Schizophr Res. View on PubMed
- 4.Comprehensive review of the rationale for davunetide in progressive supranuclear palsy, covering the molecular basis of ADNP-derived neuroprotection, preclinical evidence in tauopathy models, and the clinical development pathway. Published before the Phase II/III results were available.Gold M et al., 2012 in Neuropsychiatr Dis Treat. View on PubMed
Medical Disclaimer
This content is for educational and informational purposes only and does not constitute medical advice. The information presented reflects published research as indexed by PSI and should not be used to make treatment decisions. Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment.