Cognitive & Mood Research Moderate Evidence

NA-1 (Nerinetide)

PSD-95 inhibitor peptide studied for acute ischemic stroke neuroprotection. Designed to prevent excitotoxic neuronal death post-stroke. Phase 3 ESCAPE-NA1 trial completed with notable subgroup findings.

PSD-95strokeneuroprotectionexcitotoxicityNMDAischemianerinetide

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Half-life

4 hours IV; designed for single acute administration in stroke setting

SKUs

Evidence

Moderate Evidence

📖 What Is This?

NA-1 (nerinetide) is a neuroprotective peptide that was studied for reducing brain damage caused by stroke. It targets a pathway involved in how neurons die when blood supply is cut off. It completed a large phase 3 clinical trial, which produced nuanced results depending on treatment context — specifically whether patients received a clot-dissolving drug called tPA.

🔬 What Are Researchers Studying It For?

Ischemic Stroke Research

The ESCAPE-NA1 trial was a large phase 3 randomized trial that enrolled 1,105 patients with major ischemic stroke. All patients received endovascular treatment to remove the clot. The trial found no overall benefit of NA-1 over placebo on the primary outcome — but post-hoc analysis found that in patients who did not receive tPA, NA-1 significantly improved outcomes.

Neuroprotection Research

NA-1 was designed to interfere with a protein complex (PSD-95/NMDA receptor) that forms when neurons are starved of oxygen during stroke, accelerating their death. Blocking this complex was hypothesized to buy neurons time to survive until blood flow is restored.

Interaction with tPA

An unexpected finding in ESCAPE-NA1 was that tPA (tissue plasminogen activator) appeared to break down NA-1 rapidly, nullifying its effect. In patients who did not receive tPA, the neuroprotective signal was statistically significant. This has implications for future trial design in this space.

📊 What Does The Research Suggest?

Phase 3 ESCAPE-NA1 trial: no overall benefit vs placebo on the primary disability outcome.
Significant improvement in outcomes for the subgroup of patients who did not receive tPA.
tPA appears to degrade NA-1, explaining the interaction in the trial data.
Favorable safety profile — no increase in adverse events compared to placebo.
Further development is ongoing with trial designs that account for the tPA interaction.

⚠️ What Should You Know Before Going Deeper?

The ESCAPE-NA1 trial did not meet its primary endpoint overall, so NA-1 cannot be said to have proven efficacy for stroke. The positive subgroup finding (no-tPA patients) is a post-hoc analysis, which is hypothesis-generating rather than confirmatory. Further trials are needed to validate the subgroup finding. NA-1 is not FDA-approved.

⚙️ How It Works In The Body

When a stroke cuts off blood supply to part of the brain, neurons in that area begin dying rapidly through a process that involves calcium flooding into cells through NMDA receptors, which are normally used for learning and memory. When too much calcium rushes in, neurons activate a self-destruction sequence. NA-1 is designed to block a scaffolding protein called PSD-95 that connects NMDA receptors to the downstream cell death machinery. By interrupting that connection, NA-1 aims to let calcium still flow through the receptor while preventing the cell death cascade from activating — buying neurons time to survive until blood flow is restored by clot removal.

🛡️ Research Safety Observations

NA-1 was well-tolerated in the phase 3 trial with no increase in adverse events, hemorrhagic transformation, or safety signals compared to placebo. It is not FDA-approved. Development is continuing in trial designs that account for the tPA interaction observed in ESCAPE-NA1.

📋 Research Snapshot

Moderate Evidence

This compound has been studied in Phase 1 or Phase 2 human trials. Evidence is encouraging but more large-scale trials are needed.

Published Research Ranges

2.6mg/kg IV single dose in phase 3 trial (ESCAPE-NA1)

Research Context Only: These are ranges reported in published scientific studies for educational reference. They are not dosing recommendations. This is not medical advice. Always consult a qualified healthcare professional.

📄 Research Sources

Sources listed here are from the platform research library. All links open the original publication. No citations are generated by AI.

Nerinetide (NA-1) for Neuroprotection in Acute Ischemic Stroke: ESCAPE-NA1 Trial

The Lancet • 2020 • DOI: 10.1016/S0140-6736(19)32989-3

NA-1 (Nerinetide)

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