Protective Activity of Erythropoyetine in the Cognition of Patients with Parkinson’s Disease

Abstract

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.

NeuroEPO improves cognition in Parkinson’s disease. Preliminary report

“…Another reason to use the latent variables is to reduce the ceiling-floor effect of global screening tools such as the MMSE and the DRS, which were included, first, because MMSE is the most well-known psychometric test used to describe cognitive aging and second because the Movement Disorder Society has recommended the DRS to study cognition in PD 34 . Our preliminary report found 18 cognitive improvements in several tests (FAB, DRS, Rey figure copy and recall) in both groups (Placebo and NeuroEPO) when comparing baseline with one week and six months after the intervention. In our opinion, this could be explained partially because the first timepoint, only six weeks after the baseline, was influenced by practice and learning effects.…”

“…This molecule is similar to that produced in the brain of mammals but does not have an inducer effect in the synthesis of erythrocytes, maintaining its neuroprotective properties. NeuroEPO is safe and tolerated in healthy people 13 and PD patients 14 , but its neuroprotective effects have been mainly tested in animal models 15,16 , in-vitro models 17 , and partially reported 18 on the cognitive performance of PD patients. But this is the first attempt to study the long-term effects of cognitive effects of NeuroEPO in PD.…”

“…NeuroEPO is safe and tolerated in healthy people 13 and PD patients 14 , but its neuroprotective effects have been mainly tested in animal models 15,16 , in-vitro models 17 , and partially reported 18 on the cognitive performance of PD patients. But this is the first attempt to study the long-term effects of cognitive effects of NeuroEPO in PD.…”

The Effect of Erythropoietin and Its Derivatives on Ischemic Stroke Therapy: A Comprehensive Review

“…Furthermore, neuro-EPO improved cognitive functions in PD patients. Another clinical trial phase III with neuro-EPO treatment for PD patients is in progress to confirm its neuroprotective properties ( Pedroso et al, 2018 ). The preliminary results showed that nasally administered neuro-EPO for 5 weeks in patients with PD stages 1 and 2 on the Hoehn & Yahr Scale was well-tolerated ( García-Llano et al, 2021 ).…”

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 . In these human trials, the daily dose administered correspond to several dose of 13 μg/kg (for a man with a mean 75 kg body weight), which is close to the 40 μg/kg single dose administered to rats in this work.…”