Neuralstem, Inc. announced that it has filed an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA) to begin a phase I safety clinical trial for chronic spinal cord injury with its spinal cord stem cells. This multicenter phase I safety trial will enrol a total of 16 long-term, or chronic, spinal cord injury patients, with an American Spinal Injury Association (ASIA) Grade A level of impairment, one-to-two years post-injury. ASIA A refers to a patient with no motor or sensory function in the relevant segments and is considered to be complete paralysis.
"We are filing an application with the FDA to test our spinal cord stem cells in a second medical condition with substantial unmet needs," said Neuralstem CEO and president, Richard Garr. "The proposed trial is primarily designed to test the safety of both our cells and delivery method in chronic spinal cord injury patients."
"We are very encouraged by what we have learned transplanting the first six ALS (Amyotrophic Lateral Sclerosis) patients in our FDA-approved trial in Atlanta," said chief scientific officer and chairman of Neuralstem's Board of Directors, Karl Johe, Ph.D. "We believe that it is the right time to leverage what we have learned with ALS in spinal cord injury. We will be looking at secondary endpoints as well, by which we hope to measure some degree of functional recovery. As in the ALS trial, we are proposing to transplant patients with injuries in the thoracic (mid-back) regions first. Once the safety of the surgeries has been established, we plan to transplant patients whose injuries are in the cervical (upper spinal cord) region."
Clinical studies with chronic SCI patients have demonstrated that, even several years after motor- and sensory-complete SCI, intensive and task-specific rehabilitation can improve motor function as measured by the ASIA Impairment Scale (AIS). These clinical experiences, together with results from numerous animal studies of SCI, illustrate that even the complete, chronically-injured cord can undergo some degree of recovery and reorganization. Transplantation of Neuralstem's human spinal stem cells (HSSC) is meant to provide a neuron-rich substrate to the injured segments of a patient's spinal cord to promote further repair, regeneration, and reorganization. The goal is to harness this inherent plasticity and promote reorganization by combining stem cell transplantation with the modern concept of activity-guided rehabilitation.
Currently, no predictive animal model of chronic human SCI exists. However, in a rat model of ischemia-induced spinal cord injury that generates the condition of permanent paraplegia, transplantation of Neuralstem's HSSC into the injury site leads to significant motor recovery (reported in NEUROSCIENCE, June 29, 2007, in conjunction with the University of California at San Diego). Detailed analysis revealed robust graft survival, extensive neuronal differentiation, and integration of grafted cells into the host circuitry, all outcomes which we believe are essential for recovery of function in human patients. Similar results were obtained by Neuralstem in rodent models of ALS in which transplanted HSSC again showed extensive neuronal differentiation and integration with host neuronal circuitry, and led to the rescue of at-risk motor neuron populations (reported in Transplantation, October, 2006, and Journal of Comparative Neurology, March 2009, in conjunction with Johns Hopkins University). These studies further demonstrated that Neuralstem's HSSC transplants secreted important neuroprotective agents and extended long-distance axons into the host.
Neuralstem believes that, in chronic SCI, our HSSC transplants may promote reorganization of segmental circuitry over the long-term. In the cervical region of the spinal cord, this could result in improved breathing capacity and recovery of sensori-motor functions of the upper limbs. Segmental reorganization induced by, and utilizing graft-derived neurons, may also result in improved locomotion.
Neurons differentiated from Neuralstem's HSSC grafts in chronic thoracic injuries may serve as a bridge to connect the axons located above the site of injury to neurons of segments below the injury site. HSSC grafts may also encourage axons to regenerate through the graft to segments below the injury.
There are more than 10,000 new spinal cord injuries (SCI) in the US each year. At the time of a recent survey done by the Christopher & Dana Reeve Foundation, there were approximately 840,000 people living with chronic SCI. According to the National Spinal Cord Injury Association, 85% of SCI patients who survive the first 24 hours are still alive 10 years later.
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.