Traumatic spinal cord injury (SCI) is a catastrophic and life changing event impacting an individual’s motor and sensory function, in addition to altering involuntary functions such as breathing and bowel and bladder control. Consequently, spinal cord injury affects daily living and quality of life, and has the potential to significantly alter relationships and family functioning. Approximately 10,000 individuals sustain a traumatic spinal cord injury each year with a total of 400,000 to 450,000 individuals living with this type of injury. Statistically, young males sustain the majority of these injuries in their teens and twenties. Roughly 50% of all spinal cord injuries are termed neurologically “complete.” These severe injuries are defined by a lack of sensation or motor control in the rectal area and have essentially no neural communication between the level of injury, i.e. cervical area and the lower levels of the spinal cord. A diagnosis of neurologically complete SCI is significant in that the prognosis for recovery is poor. For example, an individual with some motor strength in their biceps muscle would likely regain some function in their wrist, but would not likely regain function in their hand, powerful triceps muscle or their lower extremities.
There is no acute treatment for spinal cord injury that has shown to be curative or significantly limit the effects of the injury and improve functional outcome. Current treatments include potential use of high dose steroids, surgical spinal stabilization and state-of-the-art rehabilitative interventions. Our spinal cord injury physicians at UMDNJ-New Jersey Medical School’s Department of Physical Medicine and Rehabilitation, in conjunction with Kessler Institute for Rehabilitation, have been selected with five other SCI centers to participate in the only Phase II clinical trial for acute spinal cord injury. This randomized, multicenter, control trial is studying the safety and efficacy of injection of macrophages directly into the damaged spinal cord to promote functional recovery. The macrophage is a white blood cell intimately involved with the inflammatory response necessary for wound healing.
The experimental therapy developed by the study sponsor, Proneuron Biotechnologies, utilizes the role of the macrophage to remove debris from the wound site and secrete growth factors, to facilitate a controlled inflammatory response and optimize wound healing. This response occurs in peripheral tissue that regenerates but is limited in the central nervous system because of the blood brain barrier. Therefore, our hypothesis is that overriding the immune privileged central nervous system by injecting macrophages directly into the spinal cord will promote wound healing and regeneration in the spinal cord, similar to that in peripheral tissues.
Prior studies using a rodent model demonstrated partial motor recovery following injection of activated macrophages into the injured spinal cord. Activation of macrophages is a proprietary technique which involves co-incubation of the blood-borne macrophages, with skin macrophages thought to be activated and involved in wound healing. Results from a Phase I clinical trial showed that three out of 10 individuals with neurologically complete spinal cord injuries, who underwent macrophage injection within 14 days from injury, demonstrated significant improvement. These three injuries became “incomplete” spinal cord injuries, as evidenced by improved sensory and motor function in the rectal area and in some cases motor function significantly below their level of injury. Incomplete injuries have a significantly better prognosis. Only 1 to 4% of all complete spinal cord injuries spontaneously evolve to incomplete injuries. An additional 33% of patients who did not change to an incomplete spinal cord injury regained additional motor and sensory function. In a follow-up Phase I study, 25% of patients became incomplete and the other 75% demonstrated some degree of recovery beyond what was predicted.
Here at UMDNJ and Kessler, we are joining with top spinal cord injury treatment centers in the country (Craig Hospital in Colorado, Mount Sinai Medical Center in New York, Shepherd Center in Atlanta, Shriner’s Children’s Hospital in Philadelphia and Sheba Medical Center in Israel) to participate in this exciting clinical trial. Our team includes myself as co-principal investigator, along with Robert Heary, MD, professor, neurosurgery, NJMS and director of the Spine Center at UMDNJ-University Hospital (UH); David Livingston, MD, Wesley J. Howe professor and Chief of Trauma Surgery, NJMS and director, New Jersey Trauma Center, UH; Steven Koltenuk, RN, study coordinator; and Steven Kirshblum, MD, professor, PM&R, NJMS and medical director, Spinal Cord Injury Program, Kessler Institute for Rehabilitation, as the overall study investigator.
Part of the excitement as well as the frustration of participating in a study of acute treatment is that our patients must receive the macrophage injection within 14 days of the study. As many of our patients have come from as far as Tennessee or Michigan, it is critical that we begin planning days after they have sustained their injuries. Additionally, these patients must have sustained a traumatic complete injury, be within the ages of 16 and 65, have a functional level of injury between the C5 motor level and the T11 level of the spinal cord and be available for one year for follow-up of their functional recovery. Perhaps the most stringent criteria are that they must have a discrete lesion within their spinal cord on MRI measuring less than 3 cm. If they qualify, there is still a one out of three chance that they will be randomized into the control group.
If our patient is randomized to the treatment arm of the study, he or she begins a two-staged procedure. The patient is brought to the OR early one morning for the harvesting of skin and blood, performed by Dr. Livingston. The skin and blood are then shipped via air or ambulance to a specialized laboratory where the macrophage cells are processed and undergo a 36-hour activation process. The “treated” cells are then shipped back and the individual returns to the OR late the following evening for spinal surgery by Dr. Heary, during which the cells are implanted directly into the spinal cord near the site of injury. The team physiatrists, Drs. Kepler and Kirshblum, along with Mr. Koltenuk, our study coordinator, perform extensive examinations to determine sensory and motor function, as well as follow-up visits at weekly, monthly and three-month intervals.
We have screened many potential candidates and enrolled six individuals at NJMS, some in treatment and some in the control group. These six join the approximately 45 patients who have enrolled to date in the overall study. As these individuals have not yet completed their year of follow-up, there is no definitive data to report, but we are hopeful. We have learned a tremendous amount from these six individuals, both from the medical and humanistic perspective. We have learned that a study of this magnitude is not possible without the commitment of many individuals and departments working together selflessly. We have learned the pitfalls and the ways to facilitate the experimental process. Most importantly, we have learned that while research demands scientific rigor and precision, there is a human factor as well as science in partnering with our patients and potential research participants. We are privileged that these individuals, in a catastrophic time in their lives, consider advancing science as well as hopefully their own outcome. We all hope this therapy will improve function for patients with the most severe of spinal cord injuries and are proud to be a part of it.
Karen Kepler, DO, PhD, is an assistant professor in the Department of Physical Medicine and Rehabilitation (PM&R) at UMDNJ-New Jersey Medical School and the director of Spinal Cord Injury Services and co-director of the Acquired Brain Injury Clinic. She received her medical degree from the UMDNJ-School of Osteopathic Medicine and completed her residency in physical medicine and rehabilitation and a fellowship in spinal cord medicine in PM&R at UMDNJ in conjunction with the Kessler Institute for Rehabilitation. Additionally, she received a PhD in neuropsychology from the City University of New York.