ROCKVILLE, Md.—Neuralstem, Inc., a Maryland-based companythat targets neurological disorders and diseases, has announced that the U.S.Food and Drug Administration (FDA) has granted approval for Neuralstem toadvance to Phase Ib in its ongoing clinical trial to test its neuroregenerativecompound, NSI-189, as a treatment for major depressive disorder (MDD).Neuralstem's technology allows them to create neural stem cells of the humanbrain and spinal cord, and it allows for control of the differentiation of thecell into mature, physiologically relevant human neurons and glia.
The Phase Ib trial will seek to determine the safety andtolerability of NSI-189 in depressed patients. The trial is a randomized,double-blind, placebo-controlled, multiple-dose escalating trial. Phase Iatested escalating doses of a single administration of the compound in healthypatients, and Phase Ib, which is expected to take approximately six months,will test the safety of escalating doses for 28 daily administrations in 24depressed patients.
"We are pleased to be approved to begin testing NSI-189in patients who suffer from depression," Karl Johe, Ph.D., ChiefScientific Officer and Chairman of Neuralstem's Board of Directors, said in apress release. "Loss of hippocampal volume is a known characteristic indepressed patients. NSI-189 stimulates neurogenesis and increases hippocampalvolume in healthy adult mice, at the same time reversing behavioral symptoms inmouse depression models, so it could address depression at the source."
NSI-189 is a proprietary compound discovered by Neuralstemthat stimulates new neuron growth in the hippocampus, the area of the brainthat plays a role in short- and long-term memory as well as spatial navigation.Damage to the hippocampus can lead to cases of anterograde amnesia, in which aperson cannot form or retain new memories, and this part of the brain isbelieved to be involved in MDD and other conditions, including Alzheimer's diseaseand post-traumatic stress disorder. The hippocampus is the first part of thebrain that Alzheimer's attacks, and as Neuralstem notes on its website,"researchers now know that depressed patients have reduced hippocampal volume."
In healthy adult mice, NSI-189 stimulated neurogenesis inthe hippocampus and significantly increased its volume. In mouse models ofdepression, the compound was shown to significantly improve behavioralresponses associated with depression, and it is hoped that in humans, it willserve to reverse the hippocampal atrophy seen in MDD and its symptoms. Both theNational Institutes of Health and the Defense Advanced Research Projects Agencyhave supported the program.
"It is exciting to see a new class of drugs thatpotentially offers a novel and different approach to this disease moving intopatients," Maurizio Fava, M.D., Slater Family Professor of Psychiatry atHarvard Medical School and Executive Vice Chair of the Department of Psychiatryat Massachusetts General Hospital, said in a press release. Fava is one of theworld's leading researchers in MDD, and helped with the design of Neuralstem'strial.
In addition to MDD, Neuralstem is also developing a celltherapy based on its technology for the treatment of amyotrophic lateral sclerosis(ALS), also known as Lou Gehrig's disease, in which the death of motor neuronsleads to paralysis. Neuralstem has received orphan status designation from theFDA for this trial. The company's cell therapy consists of transplantation ofhuman spinal cord stem cells into the gray matter of a patient's spinal cord,and in preclinical animal tests, the cells made synaptic contact with the hostmotor neurons and also expressed neurotrophic growth factors, which areprotective of cells. The company is also targeting spinal cord injury,Huntington's disease, chronic stroke and ischemic spastic paraplegia with itscell therapy platform.