Clinical trial of neuroEPO in mild‐to‐moderate Alzheimer’s disease

Abstract

Background: NeuroEPO, a nasal pharmaceutical solution of recombinant human erythropoietin with low sialic acid, was in clinical development for the treatment of mildmoderate Alzheimer's disease. Method:A double-blind, randomized, placebo-controlled, multicenter, prospective, with adaptive design, phase II/III clinical trial involving 174 patients with mild-tomoderate Alzheimer's, was conducted. NeuroEPO or placebo, with different doses, was administered by nasal route 3 times a weeks for 48 weeks. The primary outcome measure was score on the 11-item cognitive subscale of the Alzheimer's disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment). Secondary outcome measures included Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus), Global Dementia Scale (GDS), activities of daily living (ADL), hippocampal volume change over time (measured with MRI), neuropsychological scales, electroencephalography (EEG) and adverse events.Result: There were statistically significant differences between neuroEPO and placebo in median change from baseline in the primary outcome at week 48. The change in ADAS-cog11 scores final-initial (PP population) for patients in the neuroEPO 0.5 mg (n= 50, median change: -4.0), neuroEPO 1.0 mg (n=49, median change: -5.0) and placebo (n=49, median change: 4.0) groups. A difference of 8.0 points CI 95% (6.0; 10.0) neuroEPO 0.5 mg vs. placebo and 9.0 points CI 95% (6.8; 11.2) neuroEPO 1.0 mg vs. placebo at week 48, (p=0.000), was observed. Patients receiving both doses of neuroEPO also showed a significant difference in global improvement (CIBIC-Plus, p=0.000) and electroencephalography (EEG, p=0.003) compared with placebo group. About hippocampal volume change, 105 patients were analyzed. From them, 58% remained stable and 42% decline hippocampus volume. No serious adverse events related with neuroEPO were reported. Conclusion:NeuroEPO improved clinical outcomes in patients with Alzheimer's disease with good security profile. Therefore, it could be useful in the treatment of these kind of patients.

Intranasal administration of NeuroEPO does not affect the structure of respiratory mucosa in Wistar rats.

“…Recent studies have shown that NeuroEPO administered intranasally has a neuroprotective effect on different models of neurological diseases (1,2,3,4,8) . This neuroprotective effect has also been demonstrated in controlled clinical trials in Parkinson's and Alzheimer's disease (9,10) . However, it is not known whether its intranasal application at maintained doses, for a longer period, could cause alterations in the histological structure of the respiratory mucosa in rats.…”

Exploring links between 2‐oxoglutarate‐dependent oxygenases and Alzheimer's disease

“… 86 , 87 These are not optimized for delivery to the brain, which is not a major site of EPO production. Nonetheless, given that there is preliminary evidence that EPO treatment may have clinical benefit in treatment of mild to moderate AD, 88 , 89 empirically guided approaches involving boosting EPO levels/oxygen supply to the brain via use of the currently available PHD inhibitors developed for treatment of anemia by the promotion of erythropoiesis may be of interest.…”