Peptide education
Davunetide
AL-108 · NAP
Davunetide is an experimental eight-amino-acid peptide derived from activity-dependent neuroprotective protein, or ADNP. It has been studied as a nasal formulation in several neurological conditions.
A controlled study in 313 people with PSP found no difference from placebo on its two primary measures. FDA lists davunetide as not approved for PSP.
Overview
Quick answer
A laboratory hypothesis about microtubules is not the same as a proven treatment. In the largest cited trial, davunetide did not improve the two primary clinical measures in progressive supranuclear palsy, or PSP.
What did the PSP trial find?
Participants received davunetide or placebo for 52 weeks. Changes in the PSP Rating Scale and the Schwab and England Activities of Daily Living scale did not differ between groups.
Does a positive mouse result prove human benefit?
No. An alpha-synuclein mouse study reported changes in some tissue and behavioral measurements. It did not test treatment of PSP in people.
Is it approved in the United States?
FDA lists davunetide as not approved for its PSP or ADNP syndrome orphan indications. These records do not establish status for other uses or outside the United States.
What adverse effects occurred in the PSP study?
Nasal congestion, nosebleeds, and nasal discomfort were more frequent with davunetide than placebo. The trial also recorded serious events in both groups, which should not automatically be attributed to treatment.
Evidence
Evidence snapshot
Neither primary outcome favored davunetide over placebo at 52 weeks.
The primary cognitive battery did not differ significantly across groups.
Tissue and behavioral findings varied with the dose and measurement.
FDA records address PSP and ADNP syndrome, not every use or jurisdiction.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Davunetide treats progressive supranuclear palsy. | In a 52-week controlled study, both primary measures changed similarly in the davunetide and placebo groups. | The research rationale includes microtubule interaction and changes in tau measures in laboratory models. | The tested regimen did not demonstrate efficacy for PSP. |
| A small schizophrenia study established cognitive benefit. | The 63-person treated sample showed no significant treatment difference on the primary cognitive battery. A separate functional-capacity measure showed a signal across study groups. | The secondary finding is exploratory and does not establish a treatment benefit. | |
| Orphan designation is the same as drug approval. | The FDA lists a designation for ADNP syndrome and says davunetide is not approved for that orphan indication. | Designation and approval are different regulatory actions. |
Bottom line
Main takeaway
The best-studied PSP regimen did not outperform placebo on the trial's primary measures.
Nasal adverse events occurred more often with the study drug, and safety outside the studied setting remains uncertain.
A mouse alpha-synuclein model and a human PSP trial address different diseases and endpoints.
Identity
What it is
Davunetide is also called AL-108 or NAP and has the amino acid sequence NAPVSIPQ.
It is derived from ADNP, a protein studied in brain development and neuronal function.
Use context
Routes, doses, and cycle patterns
The PSP and schizophrenia trials used different nasal doses; the mouse experiment used a separate animal regimen.
Human studies and product labels
PSP clinical trial
- Purpose
- Clinical function and disease progression
- Context
- Study-reported human regimen
- Route
- Intranasal
- Amount
- 30 mg per administration
- Frequency
- Twice daily
- Duration
- 52 weeks
Neither primary measure differed from placebo in this trial.
Schizophrenia clinical trial
- Purpose
- Cognition and functional-capacity measures
- Context
- Study-reported human regimens
- Route
- Intranasal
- Amount
- 5 mg per dose in the lower-dose group; 15 mg per dose in the higher-dose group
- Frequency
- Once daily at 5 mg; twice daily at 15 mg
- Duration
- 12 weeks
Participants continued their antipsychotic treatment. The primary cognitive measure did not differ significantly between groups.
Alpha-synuclein mouse experiment
- Purpose
- Laboratory tau and behavioral measurements
- Regimen
- No single reliable dose, schedule, or cycle showed up in the materials reviewed.
- Route
- Intranasal
- Amount
- 2 or 15 mcg per mouse per administration
- Frequency
- Once daily, five days per week
- Duration
- 24 weeks
Tissue effects differed by dose and brain region; this was not a PSP trial.
What varies
- The clinical trial used a specific nasal formulation; a different product is not established as equivalent.
- The mouse experiment measured different outcomes in a different species from the clinical trials.
Research
Research evidence
The largest cited controlled trial was negative in PSP, and a smaller schizophrenia trial had a negative primary cognitive outcome.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| PSP phase 2/3 trial | 313 adults with possible or probable PSP | Randomized, double-blind, placebo-controlled | Intranasal davunetide 30 mg twice daily for 52 weeks | No significant difference in either primary clinical outcome | Results apply to the studied population and regimen | Controlled trial, negative primary endpoints |
| Schizophrenia trial | 63 treated participants continuing antipsychotic therapy | Small randomized, double-blind, placebo-controlled study | Intranasal 5 mg once daily or 15 mg twice daily for 12 weeks | No significant difference on the primary cognitive battery | A functional-capacity signal was secondary and needs confirmation | Small controlled study with negative primary outcome |
Cautions
Safety and unknowns
- In the PSP trial, nasal congestion, nosebleeds, and nasal discomfort were more common with davunetide than placebo.
- The PSP study observed serious adverse events and deaths in both groups. The study does not establish the safety of other preparations or indefinite use.
- The animal study used a different model and cannot determine human side effects or an effective human dose.
Product quality
Product identity and quality
Clinical results relate to the tested intranasal preparation and do not verify an independently marketed formulation.
Product identity
A product name alone does not verify its ingredient, strength, or formulation.
Research setting
Investigators monitored participants and used a placebo comparator in the PSP trial.
Mechanism
How it is proposed to work
Davunetide has been studied for effects on structures that help support cells, but the proposed mechanism did not translate into a positive PSP trial.
Preclinical work links the peptide to microtubules and measures of tau phosphorylation; the mouse results varied by dose and tissue.
Details
Technical details
Sources
References
- 1.
PubMed. Davunetide in patients with progressive supranuclear palsy: a randomized phase 2/3 trial
doi:10.1016/S1474-4422(14)70088-2 PMID:24873720 NCT01110720
The placebo-controlled PSP trial reported no difference on either primary endpoint.
- 2.
Schizophrenia Research. Effect of davunetide on cognition and functional capacity in schizophrenia
doi:10.1016/j.schres.2011.11.001 PMID:22169248
Full trial report: dosing schedules and no significant difference on the primary cognitive battery.
- 3.
PubMed. Intranasal davunetide and tau phosphorylation in mice overexpressing alpha-synuclein
doi:10.1002/prp2.65 PMID:25505609
Mouse experiment with dose- and tissue-specific findings, not a human clinical study.
- 4.
FDA. FDA orphan designation for davunetide in ADNP syndrome
Designation for ADNP syndrome is not approval for that indication.
- 5.
FDA. FDA orphan designation for davunetide in progressive supranuclear palsy
FDA lists davunetide as not approved for the specified PSP orphan indication. This record does not determine status for other uses or jurisdictions.