NSI-189 is a nootropic and neurogenic research chemical derived from nicotinamide and pyrazine created by Neuralstem, Inc. Research into NSI-189 has been heavily funded by the Defense Advanced Research Projects Agency (DARPA) and theNational Institutes of Health (NIH).
Molecular Formula: C22H30N4O
Structural Formula: HOOC (CH2) 7COOH
Molecular weight 366.4998 g/mol
the Food and Drug Administration (FDA) have approved the advance to Phase 1b in the ongoing clinical trial to test its neuroregenerative compound, NSI-189.
NSA-189 is a proprietary new chemical entity that stimulates new neuron growth in the hippocampus, an area of the brain believed to be contributory in MDD and other conditions, such as Alzheimer’s disease and Post-traumatic stress disorder (PTSD). Phase 1b of the clinical trial is to test the safety and tolerability of the drug in depressed patients.
Karl Johe, PhD, Chief Scientific Officer and Chairman of Neuralstem’s Board of Directors, said, “We are pleased to be approved to begin testing NSI-189 in patients who suffer from depression. Loss of hippocampal volume is a known characteristic in depressed patients. NSI-189 stimulates neurogenesis and increases hippocampal volume in healthy adult mice, at the same time reversing behavioural symptoms in mouse depression models, so it could address depression at the source.”
Maurizio Fava, MD, Slater Family Professor of Psychiatry at Harvard Medical School and Executive Vice Chair of the Department of Psychiatry at Massachusetts General Hospital, is a leading researcher into MDD and helped to design the Neuralstem trial, added, “It is exciting to see a new class of drugs that potentially offers a novel and different approach to this disease moving into patients.”
Neuralstem’s technology enabled the creation of neural stem cell lines from areas of the human CNS, including the hippocampus, a part of the brain involved in memory and the generation of new neurons. From this, Neuralstem has created virtually unlimited amounts of mature human neurons and glia in laboratory dishes which can be used to mimic the natural brain environment to test the drug’s effects.
NSI-189 is the lead compound in Neuralstem’s neuroregenerative small molecule drug platform, which the company plans to develop into orally administered drugs for MDD and other psychiatric disorders, such as anxiety, bipolar disorder, PTSD and Alzheimer’s disease. In previous tests, NSI-189 significantly improved behavioural responses associated with depression. In humans, it may reverse the human hippocampal atrophy seen in MDD and other disorders, reversing their symptoms.
The NSI-189/MDD trial is a double-blind, randomised, placebo-controlled, multiple-dose escalating trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamic effect of NSI-189 in the treatment of MDD. Phase 1a tested escalating doses of single administration in healthy patients. Phase 1b will test the safety of escalating doses for 28 daily administrations in 24 depressed patients, and will take approximately 6 months to complete.