# Study and paper trail — NeuroEPO / NeuralCIM, past and present

## Past / preclinical and early safety

- **2016 — APPSwe mouse Alzheimer’s model.** Rodríguez Cruz, Strehaiano, Rodríguez Obaya et al. reported that intranasal Neuro-EPO prevented memory deficits and amyloid toxicity in a transgenic mouse model. Evidence level: preclinical animal study.
- **2017 — healthy-volunteer safety/tolerance.** Santos-Morales et al. reported nasal NeuroEPO administration in healthy volunteers. Evidence level: early human safety/tolerability, not Alzheimer’s efficacy.
- **Parkinson’s studies.** Cuban/related teams reported short-term tolerance and preliminary cognitive signals in small Parkinson’s cohorts/trials. Evidence level: small early clinical / preliminary; not proof for Alzheimer’s or Parkinson’s disease modification.

## Present Alzheimer’s evidence

- **ATHENEA RCT, published 2023.** Phase 2–3 randomized, double-blind, placebo-controlled, multicenter Cuban trial in mild-to-moderate Alzheimer’s clinical syndrome; 174 enrolled / 170 treated. Reported median ADAS-Cog11 changes at 48 weeks: −3.0 and −4.0 in active groups vs +4.0 placebo. Authors: larger trials warranted. Evidence level: important RCT signal; needs external replication/regulatory review.
- **Post-trial observational follow-up, PubMed 2026.** Reports continued/starter NeuroEPO groups vs interruption/control groups. Evidence level: observational follow-up; less rigorous than blinded randomized trial.
- **Cuban Phase 3 / donepezil comparison registry.** Cuban registry lists a trial comparing NeuroEPO, donepezil and combination groups over 78 weeks. Evidence level: registered study; final independent publication/results should be watched.
- **University of Saskatchewan / ClinicalTrials.gov NCT07178678.** Phase 2, placebo-controlled study of NeuroEPO plus standard care for mild-to-moderate Alzheimer’s, 90 estimated participants, with Center of Molecular Immunology, Cuba as collaborator. Evidence level: future/registered independent-region study; not completed proof.

## Adjacent current science

- **Traumatic brain injury work, 2025.** NeuroEPO is being explored in preclinical TBI models. Evidence level: animal/preclinical; not a human treatment indication.
- **EPO-neuroprotection reviews.** Reviews describe erythropoietin’s neuroprotective mechanisms and translation problems: blood-brain-barrier delivery, hematopoietic/clotting risks with systemic EPO, and rationale for intranasal/non-hematopoietic variants.

## Practical meaning

The science is not empty. It has a real paper trail. But the correct current status is: promising Cuba-origin Alzheimer’s RCT plus follow-up and new trial registrations, not established mainstream therapy in Canada/U.S.