INTRODUCTION No neuroprotective treatment has been able to successfully halt the progression of Parkinson disease or prevent development of associated complications. Recombinant erythropoetin (EPO), an erythropoiesis-stimulating agent originally indicated in anemia, produced and manufactured in Cuba (iorEPOCIM, CIMAB S.A, Havana, Cuba) has neuroprotective properties. NeuroEPO is a new nasal formulation of recombinant EPO with a low content of sialic acid and without hematopoietic effects. It has neuroprotective effects in animal models.

OBJECTIVE Evaluate short-term tolerance of intranasal NeuroEPO in patients with Parkinson disease.

METHODS As part of a monocentric randomized placebo-controlled double-blind study (registered at www.clinicaltrials.gov number NCT04110678), 26 patients with Parkinson disease (stages 1 and 2 on Hoehn & Yahr Scale), were randomly divided into two groups: NeuroEPO (n = 15) and placebo (n = 11), both treated intranasally either with the drug (1 mL, at a concentration of 1 mg/mL of NeuroEPO) or placebo once a week for 5 weeks. At each application, we recorded any adverse events and blood pressure. To assess potential hematopoietic effects of the drug, hematological and biochemical variables were evaluated one week before and one week after the intervention.

RESULTS There were no significant differences (p = 0.22) between the two groups in terms of frequency of adverse events (20.0% in NeuroEPO and 9.1% in placebo groups). Three patients in NeuroEPO presented nausea, and one vomited (possibly due to the patient’s positioning during drug application). One patient in placebo group reported polyuria and nasal irritation. In both groups, the adverse events were mild, brief, required no treatment and did not present sequelae.

CONCLUSION Nasally administered NeuroEPO for five weeks in patients with Parkinson disease stages 1 and 2 on Hoehn & Yahr Scale is well tolerated.

KEYWORDS Parkinson disease, intranasal drug, neurodegenerative diseases, erythropoietin, biopharmaceutics, Cuba

INTRODUCTION Recombinant human erythropoietin is used primarily to treat anemia. There is evidence of its neuroprotective capacity from preclinical studies in Parkinson’s disease and other neurodegenerative diseases. Recombinant human erythropoietin produced in Cuba (ior-EPOCIM) is registered and approved for use in humans in Cuba and in a number of other countries.

OBJECTIVE Assess safety and possible neuroprotective effect of ior-EPOCIM in a group of Parkinson’s disease patients.

METHODS A three-phase exploratory study (proof of concept) was conducted from August 2008 to April 2009: preliminary assessment, treatment (weeks 1–5), and post-treatment (weeks 6–35). Participants were 10 Parkinson’s disease patients (8 men, 2 women) from the outpatient clinic at the International Neurological Restoration Center, all at least one year post onset, aged 47–65 years. The ior-EPOCIM was administered subcutaneously in a once-weekly dose (60 IU/kg body weight) for five weeks. Therapy with patients’ antiparkinsonian drugs was maintained throughout the study, except during motor examination, conducted following a 12-hour withdrawal (OFF condition). Safety was evaluated primarily by recording adverse events (by intensity and causality) from start of treatment until the study’s completion. Hematological parameters and blood pressure were also measured because of their direct relationship to the medication’s action. To evaluate possible neuroprotective activity, variables were included related to patients’ motor function and cognitive and affective status, measured using internationally recognized scales. All variables were evaluated before, during and after treatment. Data were processed using a fixed-effects linear model, with a repeated-measures design (significance level p ≤ 0.05).

RESULTS Three patients experienced mild adverse events (precordial discomfort and hypertension in one; leg fatigue in another; renal colic in a third), with a possible causal relationship in the first two that was neither life threatening nor required hospitalization. Hemoglobin was the only hematological parameter that showed a growing and significant increase (p < 0.001), but without reaching pathological levels. The other variables presented clinically positive and statistically significant changes compared to pretreatment assessment: motor function (p < 0.001), cognitive status (p < 0.001) and mood (p = 0.013).

CONCLUSIONS At the dosage used, ior-EPOCIM was safe and well tolerated in these Parkinson’s disease patients. Further studies are needed to corroborate these results and evaluate the medication’s possible neuroprotective effect.

KEYWORDS Parkinson disease, erythropoietin, recombinant proteins, neuroprotective agents, clinical trial, safety, ior-EPOCIM, Cuba