Significant Recovery of Motor and Neurological Functions in Ischemic Stroke Rats With NeuralStem Inc. NSI-566 Cells
Published: Oct 15, 2012
ROCKVILLE, Md., Oct. 15, 2012 /PRNewswire/ -- Neuralstem, Inc. (NYSE MKT: CUR) announced that data on Neuralstem's NSI-566 spinal cord-derived neural stem cell line in a rat model of ischemic stroke was presented in a poster, "Histopathological Assessment of Adult Ischemic Rat Brains after 4 Weeks of Intracerebral Transplantation of NSI-566RSC Cell Line," at The Society for Neurosciences Annual Meeting (http://www.sfn.org/AM2012/). This study was conducted independently in the laboratory of Dr. Cesar Borlongan, who is the director at the Center of Excellence for Aging and Brain Repair at the University of South Florida College of Medicine. Post-mortem histology was conducted in collaboration with Neuralstem. Rats that suffered ischemic stroke by middle cerebral artery occlusion, were transplanted 7 days post-stroke with increasing doses of NSI-566 into the stroke area. The animals were followed for safety and behavioral response for 56 days post-transplantation. Researchers reported Saturday that there was significant improvement in both motor and neurological tests in the stem cell-treated rats. There were significant dose-dependent differences in the behavioral improvement across treatment groups at post-transplantation periods, with the highest dose showing the most significant improvement in both motor and neurological tests. Similarly, there were significant differences in the behavioral performance among treatment groups at post-transplantation periods, with the most significant improvement in both motor and neurological tests seen at day 56 post-transplantation.
"This study was designed to evaluate the potential therapeutic value of intracerbral dosing of human neural stem cells (NSI-566, supplied by Neuralstem) in an animal model of adult ischemic stroke," said Cesar V. Borlongan, Ph.D., University of South Florida College of Medicine, and the lead study author. "The results are very clear. The recovery of motor and neurological tests demonstrated by high-dose transplanted stroke animals was significantly better throughout the 56-day study period compared to vehicle-infused stroke animals, or low-dosed animals. In addition, there was stable improvement in the high-dose animals, and they showed a trend of better improvement over time."
A separate poster, "Survival and Differentiation of Human Neural Stem Cells (NSI-566RSC) After Grafting into Ischemia-Injured Porcine Brain," was also presented on Saturday. This study was independently carried out by Dr. Martin Marsala and his colleagues. Dr. Marsala is a professor and the head of the Neuroregeneration Laboratory at University of California San Diego and also a member of the Sanford Consortium for Regenerative Medicine. In this study, the same stem cells were transplanted into the brains of pigs that received an ischemic stroke on one side of the brain. 8-9 weeks after the ischemic event, which models chronic stroke in humans, feasibility and safety of escalating cell doses and injections were assessed. Body temperature, behavior, muscle tone and coordination, sensory function, food consumption, defecation, and micturition were monitored at least twice daily for the first 7 days, and once weekly thereafter, until termination. Up to 12 million cells in 25 cell injection deposits via 5 cannula penetrations were shown to be safe, which closely mimics the intended clinical route and method of delivery in future human clinical trials. At 6 weeks post-transplantation, there were no complications from the cell transplantation method or the cells. All animals recovered and showed progressive improvement with no distinction. All treated animals showed effective engraftment and neuronal maturation with extensive axonal projections. These data support the application of NSI-566RSC cell line to be transplanted into a chronic stage of previously ischemia-injured brain for treatment of motor deficits resulting from stroke.
"Our study was designed to evaluate the potential value of Neuralstem's cells in a chronic model of ischemic stroke and in a species that allowed for the use of human scale transplantation tools and dosing," said Martin Marsala, MD, at the University of California at San Diego Medical School, and the lead study author of the porcine study. "We have demonstrated clearly that both the route of administration and the cells are safe and well tolerated and that the cells survived and differentiated into mature neurons in the host brain tissue."
"We have demonstrated safety and efficacy of NSI-566RSC in a subacute model of ischemic stroke in rats and feasibility and safety in a chronic model of ischemic stroke in mini-pigs," said Karl Johe, PhD, Chairman of Neuralstem's Board of Directors and Chief Scientific Officer. "Together, these two studies demonstrate strong proof of principle data that our NSI-566 cells are ready to go into humans to treat paralysis in stroke patients."
Neuralstem has recently completed a Phase I trial testing the safety of NSI-566 in the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) and has been approved to initiate a human clinical trial in ischemic stroke in China, through its subsidiary, Suzhou Neuralstem.
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. Neuralstem has recently treated the last patient in an FDA-approved Phase I safety clinical trial for amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig's disease, and has been awarded orphan status designation by the FDA.
In addition to ALS, the company is also targeting major central nervous system conditions with its NSI-566 cell therapy platform, including spinal cord injury, ischemic stroke and glioblastoma (brain cancer). The company has submitted an IND (Investigational New Drug) application to the FDA for a Phase I safety trial in spinal cord injury.
Neuralstem also has the ability to generate stable human neural stem cell lines suitable for the systematic screening of large chemical libraries. Through this proprietary screening technology, Neuralstem has discovered and patented compounds that may stimulate the brain's capacity to generate new neurons, possibly reversing the pathologies of some central nervous system conditions. The company is in a Phase Ib safety trial evaluating NSI-189, its first neurogenic small molecule compound, for the treatment of major depressive disorder (MDD). Additional indications could include chronic traumatic encephalopathy (CTE), Alzheimer's disease, and post-traumatic stress disorder (PTSD).
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Cautionary Statement Regarding Forward Looking Information
This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding potential applications of Neuralstem's technologies constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstem's periodic reports, including the annual report on Form 10-K for the year ended December 31, 2011 and the quarterly report on Form 10-Q for the period ended June 30, 2012.
SOURCE Neuralstem, Inc.