Protein–energy malnutrition affects one in nine people worldwide and is most prevalent among children aged less than five years in low-income countries. Early childhood malnutrition can have damaging neurodevelopmental effects, with significant increases in cognitive, neurological and mental health problems over the lifespan, outcomes which can also extend to the next generation. This article describes a research collaboration involving scientists from five centers in Barbados, China, Cuba and the USA. It builds on longer-term joint work between the Barbados Nutrition Study (which, over a 45-year span, has extensively documented nutritional, health, behavioral, social and economic outcomes of individuals who experienced protein–energy malnutrition in the first year of life and healthy controls from the same classrooms and neighborhoods) and the Cuban Neuroscience Center (which has developed low-cost brain imaging methods that can be readily used in low income settings to identify biomarkers for early detection and treatment of adverse consequences of childhood malnutrition).

This collaboration, which involved Barbadian, Cuban and US scientists began in the 1970s, when quantitative EEG techniques were applied to EEG data collected in 1977–78, at which time study participants were aged 5–11 years. These EEG records were never fully analyzed but were stored in New York and made available to this project in 2016. These data have now been processed and analyzed, comparing EEG findings in previously malnourished and control children, and have led to the identification of early biomarkers of long-term effects of early childhood protein–energy malnutrition. The next stage of the project will involve extending earlier work by collecting EEG recordings in the same individuals at ages 45–51 years, 40 years later, and comparing findings to earlier data and to these individuals’ behavioral and cognitive outcomes. Quantitative EEG biomarkers of the effects of protein–energy malnutrition may help identify children at greatest risk for early malnutrition’s adverse neurodevelopmental effects and inform development of targeted interventions to mitigate the long-term adverse effects of protein–energy malnutrition in developing countries.

KEYWORDS Protein–energy malnutrition, electroencephalography, EEG, biomarkers, neurosciences, Barbados, Cuba, USA

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