Neuralstem, Inc. has started dosing the second cohort of patients in its ongoing phase Ib to test the safety of NSI-189 in the treatment of major depressive disorder (MDD). NSI-189, the lead compound in neurogenic small molecule platform, is a proprietary new chemical entity that stimulates new neuron growth in the hippocampus, a region of the brain believed to be implicated in MDD, as well as other diseases and conditions such as: chronic traumatic encephalopathy (CTE), Alzheimer's disease, and post-traumatic stress disorder (PTSD).

"We are pleased that the second cohort of depression patients has begun treatment," said Karl Johe, PhD, chairman of the Board and chief scientific officer of Neuralstem. Johe further added, "There were no adverse, clinically significant findings in vital signs, respiration rate, pulse, body temperature readings, blood/urine tests, ECG, EEG, C-SSRS, or MRI in the first cohort. PK analysis showed the expected range of drug metabolism. In short, there were no surprises. The 40mg QD dose for 28 days was well-tolerated and safe. I expect the same from the next dose group, 40mg BID for 28 days.  The efficacy data is, of course, blinded for all cohorts until the end of the trial.”

Neuralstem's patented technology enables the creation of neural stem cell lines from many areas of the CNS, including the hippocampus. The hippocampus is a part of the brain involved in memory and the generation of new neurons. It is also implicated in several major neurological and psychiatric diseases. From its hippocampal neural stem cell lines, Neuralstem has created virtually unlimited amounts of mature neurons and glia in laboratory dishes. These can be used to mimic the natural brain environment in order to test drug effects.

Neuralstem has been engaged in a drug discovery programme with these hippocampal stem cell lines since 2000. In 2009, Neuralstem was granted US patents on four first-in-class chemical entities that boost the generation of new neurons. NSI-189, the first of these to be in a clinical trial, significantly stimulates the generation of new hippocampal neurons (neurogenesis) in vitro and in animal models.

NSI-189 is the lead compound in Neuralstem's neurogenic small molecule drug platform, which the company plans to develop into orally administered drugs for MDD and other psychiatric and cognitive disorders as diverse as CTE, Alzheimer's disease, and PTSD.

NSI-189 has been shown to stimulate neurogenesis of human hippocampus-derived neural stem cells in-vitro and in vivo. In healthy normal adult mice, NSI-189 stimulated neurogenesis in the hippocampus and significantly increased its volume, apparently by increasing its synaptic network after 28 days of daily oral administration. In mouse models of depression, NSI-189 significantly improved behavioral responses associated with depression. In humans, NSI-189 may reverse the human hippocampal atrophy seen in MDD and other disorders and reverse their symptoms. This program has received significant support from both the Defense Advanced Research Projects Agency (DARPA)and the National Institutes of Health (NIH).

The NSI-189/MDD trial is a randomized, double-blind, placebo-controlled, multiple-dose escalating trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamic effect of NSI-189 in the treatment of MDD. Phase Ia tested escalating doses of single administration of NSI-189 in healthy patients. Phase Ib is testing the safety of escalating doses of NSI-189 for 28 daily administrations in 24 depressed patients. The phase Ib portion of the trial is expected to take approximately six months to complete.