Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans. A phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days (Group A) or 0.5 mg of NeuroEPO (Group B) with the same schedule. The working hypothesis was that intranasal NeuroEPO produce <10% of severe adverse reactions in the evaluated groups. Therefore, a rigorous assessment of possible adverse events was carried out, which included tolerance of the nasal mucosa and the effect on hematopoietic activity. Clinical safety evaluation was daily during treatment and laboratory tests were done before and on days 5 and 14 after starting treatment. Twenty-five volunteers, 56% women, with a mean age of 27 yrs. were included. Twelve of them received the highest NeuroEPO dose. Twenty types of adverse events occurred, with headache (20%) and increase of hepatic enzymes (20%) as the most reported ones. Nasopharyngeal itching was the most common local event but only observed in four patients (16%), all of them from the lowest dose group. About half of the events were very probably or probably caused by the studied product. Most of the events were mild (95.5%), did not require treatment (88.6%) and were completely resolved (81.8%). No severe adverse events were reported. During the study the hematopoietic variables were kept within reference values. NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. Cuban Public Registry of Clinical Trials RPCEC00000157 , June 10, 2013.

Introduction: Treatment strategies in Parkinson’s disease (PD) can improve a patient’s quality of life but cannot stop the progression of PD. We are looking for different alternatives that modify the natural course of the disease and recent research has demonstrated the neuroprotective properties of erythropoietin. In Cuba, the Center for Molecular Immunology (CIM) is a cutting edge scientific center where the recombinant form (EPOrh) and recombinant human erythropoietin with low sialic acid (NeuroEPO) are produced. We performed two clinical trials to evaluate the safety and tolerability of these two drugs in PD patients. In this paper we want to show the positive results of the additional cognitive tests employed, as part of the comprehensive assessment. Materials and method: Two studies were conducted in PD patients from the outpatient clinic of CIREN, including n = 10 and n = 26 patients between 60 and 66 years of age, in stages 1 to 2 of the Hoehn and Yahr Scale. The first study employed recombinant human (rhEPO) and the second an intranasal formulation of neuroEPO. All patients were evaluated with a battery of neuropsychological scales composed to evaluate global cognitive functioning, executive function, and memory. Results: The general results in both studies showed a positive response to the cognitive functions in PD patients, who were undergoing pharmacological treatment with respect to the evaluation (p < 0.05) before the intervention. Conclusions: Erythropoietin has a discrete positive effect on the cognitive functions of patients with Parkinson’s disease, which could be interpreted as an effect of the neuroprotective properties of this molecules. To confirm the results another clinical trial phase III with neuroEPO is in progress, also designed to discard any influence of a placebo effect on cognition.