Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study

Abstract

BackgroundDelivery 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.MethodsA 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.ResultsTwenty-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.ConclusionsNeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers.Trial registrationCuban Public Registry of Clinical Trials RPCEC00000157, June 10, 2013.

Detection of a nonerythropoietic erythropoietin, Neuro‐EPO, in blood after intranasal administration in rat

“…In human, a first evaluation on healthy human volunteers 27 indicated that 0.5 and 1 mg of Neuro‐EPO every 8 h during 4 days were well tolerated and had no erythropoiesis effect. More clinical trials at similar dosage are ongoing against stroke (acute treatment 1‐mg Neuro‐EPO by nasal route every 8 h for 3 days) and against long‐term neurodegenerative disease on mild–moderate Alzheimer patients and Parkinson patients 28,29 .…”

Erythropoietin and Friedreich Ataxia: Time for a Reappraisal?

“…Further advances have been made also concerning administration route. Intranasal formulations of EPO and EPO-analogs have been developed in order to avoid repeated injections or high-dose systemic administration (Genc et al, 2011; Santos-Morales et al, 2017). Indeed, the nasal route can bypass the blood brain barrier with an optimal distribution in the cerebrospinal fluid and negligible flow in the systemic circulation, thus potentially hampering unwanted side effects (Genc et al, 2011).…”

Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury

“…There are already a few clinical studies exploring the intranasal route for a variety of inflammatory acute and chronic neurological conditions that require considerable systemic exposure . These studies are summarized in Table .…”