Virtual Therapy with the NMDA Antagonist Memantine in Hippocampal Models of Moderate to Severe Alzheimer’s Disease, in Silico Trials

Abstract

The variability in clinical trial results on memantine treatment of Alzheimer’s disease remains incompletely explained. The aim of this in silico study is a virtual memantine therapy for Alzheimer’s disease that provides a different perspective on clinical trials; An in silico randomised trial using virtual hippocampi to treat moderate to severe Alzheimer’s disease with doses of memantine 3–30 µM compared to placebo. The primary endpoint was the number of impulses (spikes). Secondary endpoints included interspike interval and frequency; The number of virtual moderate-AD hippocampal spikes was significantly lower, at 1648.7 (95% CI, 1344.5–1952.9), versus those treated with the 3 µM dose, 2324.7 (95% CI, 2045.9–2603.5), and the 10 µM dose, 3607.0 (95% CI, 3137.6–4076.4). In contrast, the number of virtual spikes (spikes) of severe AD of the hippocampus was significantly lower, at 1461.8 (95% CI, 1196.2–1727.4), versus those treated with the 10 µM dose, at 2734.5 (95% CI, 2369.8–3099.2), and the 30 µM dose, at 3748.9 (95% CI, 3219.8–4278.0). The results of the analysis of secondary endpoints, interspike intervals and frequencies changed statistically significantly relative to the placebo; The results of the in silico study confirm that memantine monotherapy is effective in the treatment of moderate to severe Alzheimer’s disease, as assessed by various neuronal parameters.