Discussion
diarrhea, gastrointestinal adverse, abdominal pain, torsades de pointes, depression, hematological toxicity, dizziness, Alzheimer’s clinical syndrome, nausea,, headache, MRI-detectable ARIA, sinoatrial and atrioventricular block, nausea, vomiting, AD, anorexia, migraine, Alzheimer
DISEASE PROGRESSION, BRAIN ATROPHY, SEVERE SINUS BRADYCARDIA, ADVERSE EVENTS, TORSADES DE POINTES, SECONDARY, MIGRAINE, EVENTS, ANOREXIA, ALZHEIMER
In this phase 2–3 trial, neuroEPO plus groups slowed the Alzheimer’s clinical syndrome progression, based on the ADAS-Cog11 score, compared with placebo and across secondary clinical outcomes including CIBIC+, GDS, MoCA, NPI, and cerebral perfusion.NeuroEPO plus treatment resulted in a clinically meaningful benefit (considered as the minimum of a clinically important effect of 4 points in the primary end point of the ADAS-Cog11 score) [Additionally, 69.9% of the patients receiving neuroEPO plus improved the CIBIC+ while 98.2% of the placebo patients worsened the CIBIC+ score. Furthermore, an estimated 92.9% of participants receiving neuroEPO plus groups had no change in the GDS at 48 weeks (no disease progression), compared with 69.4% of participants receiving placebo.In our trial, the adjusted absolute difference in the changes between the neuroEPO plus groups and placebo group goes far beyond the initial hypothesis.The potential benefit of anti-Aβ drugs to cognition in AD remains under active debate [Perhaps this discrete benefit is due to the fact that these drugs have been directed at a single target. Something similar happens with other previously registered medications [NeuroEPO plus treatment shows good results for both moderate and mild stage (Table S6 and Fig. S7, In our patient set, the frequency of subject with APOE ε4 allele positive was lower than the reported in literature for patients with a definitive diagnostic of AD (47% vs. greater than 60%) [Cerebral perfusion measured by SPECT is a non-invasive image diagnosis method used to evaluate functional parameters of brain and is typically reduced in Alzheimer patients. Flow reduction in the posterior temporoparietal regions is particularly relevant [At baseline, the HC volume measured by MRI was significantly lower (Changes in vMRI showed that the HC volume was independent of the ADAS-Cog11 score at baseline. However, the finding that the magnitude of the percent change was significant at 48 weeks in the placebo group is important, and additional trials with a larger sample size and over a longer period of time are needed to evaluate this aspect.NeuroEPO plus treatment shows a very good safety profile, especially when compared with other drugs approved for the treatment of AD, where a greater number of adverse events, many of them serious, have been reported [Oral administration of AChEIs (donepezil, galantamine, and rivastigmine) increases gastrointestinal adverse effects, such as abdominal pain, nausea, vomiting, diarrhea, and poor appetite. Also, older adults treated with AChEIs are at greater risk of cardiovascular side effects such as sinoatrial and atrioventricular block, severe sinus bradycardia, and QT interval prolongation with torsades de pointes [Some gastrointestinal and nervous system side effects such as nausea, vomiting, diarrhea, anorexia, dizziness, depression, and headache were observed with the use of memantine [Anti-Aβ drugs cause MRI-detectable ARIA. These side effects are often clinically silent or are associated with non-life threating symptoms such as migraine that resolve over 3–4 months of treatment suspension. In severe cases, ARIA may require hospitalization and some patients interrupt treatment. A meta-analysis revealed the potential for anti-Aβ therapies to compromise long-term brain health by accelerating brain atrophy [In our trial, the majority of adverse events reported, were mild and no related with neuroEPO plus treatment. The drug was well tolerated and no serious related events were reported. NeuroEPO plus is a derivative of EPO, which is known to cause hematological toxicity. During trial, the behavior of the hematological parameters was carefully evaluated. Hemoglobin slightly decreased over time in the three groups, but within the normal values, with no statistically significant differences between the groups or over time. Therefore, intranasal administration of neuroEPO plus did not cause any sign of hematological toxicity. These safety results are consistent with previous clinical trials [