NSI-189’s Method of Action
Although it has been demonstrated in rats and chimps, the suggestion that having too small of a hippocampus causes depression and other diseases in humans is still technically just a theory. NSI-189 increases hippocampal volume in adult mice by 20%, a region of the brain that is one of the first to suffer damage resulting in memory loss, disorientation, encephalitis, and hypoxia from disease’s such as Alzheimer’s .
Tests have shown that NSI-189 significantly improved behavioral responses that are associated with depression (6). In humans it may counter hippocampal atrophy which is seen in disorders such as MDD, reversing their symptoms. A phase 1B randomized, double-blind, placebo-controlled, multiple-dose escalation study conducted over a 28 day period showed behavioral efficacy in 24 patients who were orally administered NSI-189 . The efficacy measurements showed a clinically meaningful reduction in cognitive and depressive symptoms across all measures, and appeared to persist over time during follow up for the efficacy assessments which included the Clinical Global Impression – Improvement (CGI-I), Montgomery-Aserb Depression Rating Scale (MADRS), Cognitive and Physical Functioning Questionnaire (CPFQ, and the Symptoms of Depression Questionnaire (SDQ)
Phase 1A tested escalating doses of the neurogenic compound NSI-189 in healthy patients, 1B tested the safety of escalating doses in 24 depressed patients over the course of 28 days . During phase 1B patients were administered 40 mg per day, and 80 mg per day, and at the highest dose 120 mg per day. No serious adverse events occurred during the time of the study and the drug was well tolerated. Reduction in cognitive and depressive symptoms were observed across all measures for the two lower doses 40 mg/day and 80 mg/day but not for the highest dose 120 mg/day