Medically reviewed content based on the official product characteristics document and published clinical research.
Introduction
Alzheimer’s disease is the most common cause of dementia worldwide, progressively affecting memory, thinking, behavior, and the ability to perform everyday activities. According to the World Health Organization, Alzheimer’s disease contributes to approximately 60% to 70% of all dementia cases globally. Who.IN/ Dementia (opens in a new tab)
Despite decades of research, available therapies have traditionally focused on symptom management rather than directly protecting brain cells from degeneration. This has led researchers to investigate novel neuroprotective approaches that may help preserve neuronal function and support brain repair.
One such emerging therapy is NEURALCIM® (NeuroEPO Plus), a low-sialic acid recombinant human erythropoietin administered through the nasal cavity. Unlike conventional erythropoietin formulations used to treat anemia, NEURALCIM® has been specifically engineered to target the central nervous system and exert neuroprotective effects without significant erythropoietic activity. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab), pmc.ncbi.nlm.nih.gov (opens in a new tab)
Recent clinical evidence suggests that NEURALCIM® may offer meaningful cognitive benefits for patients with mild-to-moderate Alzheimer’s disease while maintaining a favorable safety profile. pmc.ncbi.nlm.nih.gov (opens in a new tab), springer.com (opens in a new tab)
What Is NEURALCIM®?
NEURALCIM® (NeuroEPO Plus) is an intranasal formulation containing low-sialic acid recombinant human erythropoietin (EPO). The product was developed by the CENTER FOR MOLECULAR IMMUNOLOGY in Havana, Cuba, and is approved in Cuba for the treatment of mild-to-moderate Alzheimer’s disease under specialist supervision. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Product Overview
- Brand Name: NEURALCIM®
- Active Ingredient: Low-sialic acid recombinant human erythropoietin
- Strength: 1 mg/mL
- Dosage Form: Nasal instillation solution
- Indication: Mild-to-moderate Alzheimer’s disease
- Route of Administration: Intranasal
- Storage Requirements: 2°C to 8°C; protect from light; do not freeze
- Prescription Status: Specialist physician supervision required
[SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Why the Intranasal Route Matters
One of the major challenges in treating neurological diseases is the blood-brain barrier (BBB), a highly selective protective system that restricts many medications from entering the brain.
NEURALCIM® was specifically developed for intranasal administration because low-sialic acid erythropoietin undergoes rapid degradation when administered systemically. Delivering the therapy through the nasal cavity allows the molecule to reach the central nervous system while bypassing much of the liver’s metabolism. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Scientific literature has demonstrated that intranasal administration can provide a direct pathway from the nasal cavity to the brain through olfactory and trigeminal pathways, making it an increasingly attractive approach for treating neurological conditions. National Library of Medicine (opens in a new tab).
Animal studies referenced in the product dossier demonstrated that intranasally administered NeuroEPO reached brain tissue, including the olfactory bulbs and cerebellum. Studies in non-human primates also showed increased erythropoietin concentrations in cerebrospinal fluid shortly after administration. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
How NEURALCIM® Works
Unlike many Alzheimer’s therapies that target a single disease mechanism, NEURALCIM® appears to influence multiple pathways involved in neurodegeneration.
According to the product characteristics document, NEURALCIM® acts as a neuroprotective agent through several mechanisms. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Prevention of Neuronal Cell Death
The therapy activates signaling pathways that inhibit apoptosis, the programmed death of neurons that contributes to cognitive decline in Alzheimer’s disease. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Reduction of Neuroinflammation
Chronic inflammation is increasingly recognized as a key contributor to Alzheimer’s disease progression. Preclinical studies demonstrated that NeuroEPO reduced markers of neuroinflammation in animal models of Alzheimer’s disease. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab), National Library of Medicine (opens in a new tab).
Protection Against Oxidative Stress
Oxidative stress contributes significantly to neuronal injury in Alzheimer’s disease.
NEURALCIM® has been shown to increase levels of:
- Brain-Derived Neurotrophic Factor (BDNF)
- Glutathione-S-transferase (GST)
Both play important roles in neuronal survival and protection from oxidative damage. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Promotion of Neuroplasticity
The therapy may support:
- Neurogenesis
- Synaptic repair
- Functional recovery
- Neuroplasticity
These processes are essential for maintaining and restoring cognitive function. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Vascular and Endothelial Protection
NEURALCIM® also promotes:
- Angiogenesis
- Capillary extension
- Endothelial protection
Healthy cerebral circulation is increasingly recognized as an important factor in preserving cognitive health. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Clinical Evidence: The ATHENEA Trial
The strongest evidence supporting NEURALCIM® currently comes from the published ATHENEA randomized clinical trial, published in the journal Alzheimer’s Research & Therapy in 2023. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab).
Study Design
The ATHENEA trial was:
- Phase II/III
- Randomized
- Double-blind
- Placebo-controlled
- Multicenter
It enrolled 174 patients with mild-to-moderate Alzheimer’s disease, of whom 170 received treatment. Participants were randomized to receive:
- NeuroEPO Plus 0.5 mg
- NeuroEPO Plus 1.0 mg
- Placebo
Treatment was administered intranasally three times weekly over a 48-week period. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)
Primary Cognitive Outcomes
Researchers evaluated cognitive performance using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11).
After 48 weeks:
- The 0.5 mg NeuroEPO Plus group demonstrated a median ADAS-Cog11 improvement of −3.0 points.
- The 1.0 mg NeuroEPO Plus group demonstrated a median improvement of −4.0 points.
- The placebo group experienced worsening cognition with a median change of +4.0 points.
Both treatment groups achieved statistically significant improvements versus placebo. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)
Secondary Outcomes
The study also demonstrated significant improvements in:
- Global clinical status
- Montreal Cognitive Assessment (MoCA)
- Neuropsychiatric symptoms
- Brain perfusion measures
compared with placebo-treated participants. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)
The authors concluded:
Among participants with mild-to-moderate Alzheimer’s disease, NeuroEPO Plus improved cognitive outcomes at 48 weeks and demonstrated a very good safety profile. Larger studies are warranted to further establish efficacy and long-term safety. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)
Safety Profile
The available evidence suggests that NEURALCIM® is generally well tolerated.
According to the official product information:
- Most adverse events were mild.
- Most were reversible.
- Most did not require treatment discontinuation.
- No serious treatment-related adverse reactions were identified during clinical development.
[SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Most Frequently Reported Side Effects
Reported adverse reactions included:
- Headache
- Nausea
- Sneezing
- Nasal burning
- Nasopharyngeal irritation
- Elevated blood pressure
- Elevated alanine aminotransferase (ALT)
[SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
In the Alzheimer’s disease study population, adverse events were infrequent, and the vast majority were considered unrelated to treatment. The only event considered potentially related to treatment was numbness of the right upper limb. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
The ATHENEA trial similarly reported a favorable safety profile throughout the 48-week study period. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)
Contraindications and Special Precautions
NEURALCIM® should not be used in patients with known hypersensitivity to the active ingredient or similar biological compounds. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Additional precautions include:
- Administration under medical supervision
- Careful monitoring in patients with chronic rhinitis
- Use immediately after opening because the formulation contains no preservatives
- Maintenance of clear airways before administration
[SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Important Note: The approved product information does not identify cancer or previous malignancy as a formal contraindication. However, specialist assessment remains essential for determining treatment eligibility, and additional clinical considerations may be applied on an individual basis during patient evaluation. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Drug Interactions
The official prescribing information identifies one notable interaction:
Zinc Sulfate
Concurrent use of zinc sulfate may reduce the therapeutic effect of NEURALCIM®. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
No significant interactions were observed during clinical studies involving:
- Vitamins
- Antihypertensives
- Diuretics
- Tricyclic antidepressants
- Hypoglycemic medications
[SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Administration Guide
Figure 1: Patient Positioning
[Insert Figure 1 from the product document here]
Caption: Patient positioned supine with the head tilted backward approximately 45 degrees to facilitate delivery toward the upper nasal cavity. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Figure 2: Dose-Limiting Device Placement
[Insert Figure 2 from the product document here]
Caption: Placement of the supplied dose-limiting device before administration. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Figure 3: Intranasal Administration Technique
[Insert Figure 3 from the product document here]
Caption: Correct administration technique using the supplied syringe after needle removal. The dose is delivered slowly into each nostril according to prescribing instructions. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Recommended Dosage
For mild-to-moderate Alzheimer’s disease:
- 0.5 mg administered intranasally
- Three times weekly
- On alternate days
Each treatment dose is divided equally between both nostrils:
- 0.25 mL in one nostril
- 0.25 mL in the opposite nostril
[SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Frequently Asked Questions
Is NEURALCIM® a cure for Alzheimer’s disease?
No. Current evidence does not indicate that NEURALCIM® cures Alzheimer’s disease. Rather, it is designed to help protect neurons, support brain repair mechanisms, and potentially slow cognitive decline while improving cognitive performance in some patients. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab), [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
How long does treatment continue?
The ATHENEA clinical trial evaluated treatment over 48 weeks, while prescribing decisions in clinical practice should be determined by the treating specialist. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)
Does NEURALCIM® require hospitalization?
No. According to the prescribing information, treatment can be administered on an outpatient basis under physician supervision. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab)
Is the therapy supported by clinical evidence?
Yes. In addition to the manufacturer’s prescribing information, a peer-reviewed Phase II/III randomized clinical trial demonstrated statistically significant cognitive benefits compared with placebo in patients with mild-to-moderate Alzheimer’s disease. National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)
Conclusion
NEURALCIM® represents a novel neuroprotective therapeutic approach for mild-to-moderate Alzheimer’s disease. By leveraging intranasal delivery and a low-sialic acid recombinant erythropoietin formulation, the therapy is designed to reach the central nervous system efficiently while activating multiple mechanisms associated with neuronal survival, neuroplasticity, reduced oxidative stress, and reduced neuroinflammation. [SUMMARY OF…T FEATURES | PDF] (opens in a new tab), National Library of Medicine (opens in a new tab)
Importantly, the publication of the ATHENEA Phase II/III randomized clinical trial provides independent peer-reviewed evidence supporting improvements in cognitive outcomes and demonstrating a favorable safety profile in patients with Alzheimer’s disease. While additional large-scale studies are warranted, the currently available evidence positions NEURALCIM® as one of the more promising emerging neuroprotective therapies in the evolving landscape of Alzheimer’s disease treatment., National Library of Medicine (opens in a new tab), springer.com (opens in a new tab)