The US Food and Drug Administration (FDA) has approved to advance phase Ib in ongoing clinical trial to test Neuralstem, Inc's novel neuroregenerative compound, NSI-189, for the treatment of major depressive disorder (MDD). Phase I b will test the safety and tolerability of the drug in depressed patients.

NSI-189 is a proprietary new chemical entity discovered by Neuralstem that stimulates new neuron growth in the hippocampus, an area of the brain that is believed to be involved in MDD as well as other diseases and conditions, such as Alzheimer's disease and post-traumatic stress disorder (PTSD).

“We are pleased to be approved to begin testing NSI-189 in patients who suffer from depression,” said Karl Johe, PhD, chief scientific officer and chairman of Neuralstem's Board of Directors. “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.”

“It is exciting to see a new class of drugs that potentially offers a novel and different approach to this disease moving into patients,” said 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. Dr Fava, one of the world's leading researchers in MDD, helped design the Neuralstem trial.

Neuralstem's technology enabled the creation of neural stem cell lines from many areas of the human 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 human neurons and glia in laboratory dishes. These can be used to mimic the natural brain environment in order to test drug effects.

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, above and beyond the neural stem cells' innate differentiation.

NSI-189 stimulated neurogenesis of human hippocampus-derived neural stem cells in-vitro. 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 behavioural 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 Defence 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 will test 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.

Neuralstem's patented technology enables the ability to produce neural stem cells of the human brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glia.