Neuralstem Cell Therapy
for Spinal Cord Injury
- Product status:
- U.S.: FDA-approved NSI-566/cSCI Phase I Safety Clinical Trial completed the last surgery in July 2015, with six-month post-observation period; FDA amended protocol to four patients total
- South Korea: NSI-566/Acute SCI Phase I/II trial awaiting IND approval
- Mechanism of Action: Rebuilding neural circuitry across and below the injury site
- Route of Administration: Direct injections into the spinal cord in and around the injury site
According to the National Spinal Cord Injury Association, three classes of neural tissue damage leading to paralysis have been identified:
- Nerve cell death within the spinal cord
- Disruption of nerve pathways
- Demyelination, or destruction of the protective insulation surrounding axons, which conduct nerve signals
Recent clinical work has indicated that intensive rehabilitation can improve motor function in spinal cord injury patients even several years post injury. Neuralstem’s NSI-566 neural stem cells could provide a neuron-rich substrate to the injured spinal cord segments, possibly promoting and supporting repair, regeneration and reorganization.
Neuralstem is seeking to treat the symptoms of spinal cord injury via transplantation of its cells directly into the gray matter of the patient’s spinal cord. Neuralstem expects its cells will integrate into a patient’s own neural tissue and possibly create new circuitry to help transmit nerve signals to muscles. Specifically, neurons differentiated from these grafts may serve as a bridge to connect the axons located above the injury site to neurons of segments below the injury. The transplanted cells may also promote reorganization of the spinal cord segmental circuitry over time, possibly leading to improved motor function.
In preclinical work, rats with ischemia-induced spinal cord injury recovered a significant amount of motor function after transplantation with Neuralstem cells. View published paper here. In another study, rats with surgically transected spinal cords, which rendered them permanently and completely paraplegic, were reported to recover significant locomotor function, regaining movement in all lower extremity joints. View scientific journal CELL report here. Additionally, a published study showed that rats transplanted with NSI-566 cells, three days after a spinal cord injury (acute), showed improvement along several measures of motor function and a reduction of spasticity. View published paper here.
Neuralstem cells also express powerful nerve growth factors that are essential to the healthy function of the central nervous system (CNS). These could protect the patient’s own neurons from further degeneration due to injury.
Neuralstem Spinal Cord Injury Trial
Neuralstem completed the final surgery in a Phase I safety trial of its NSI-566 neural stem cells for chronic spinal cord injury (cSCI) at the University of California, San Diego School of Medicine, supported and funded by the UC San Diego Sanford Stem Cell Clinical Center, in July 2015. This phase of the trial will conclude after a six-month post-surgery observation period of the last patient.
In October 2015, Joseph Ciacci, M.D., UCSD School of Medicine, presented initial NSI-566/cSCI
Phase I safety data. Dr. Ciacci reported that there had been no serious adverse events; that implantation of stem cells in cSCI patients is feasible, and that implantation of stem cells in the spinal cord injury patients has been safe and well tolerated.
The FDA had amended the Phase I trial protocol to a total of four patients, due to the safety of the same cells and similar procedure, proven in Neuralstem’s NSI-566/ALS trials. The four cSCI patients, with thoracic spinal cord injuries (T2-T12), have an American Spinal Injury Association (AIS) grade A level of impairment one-to-two years post-injury. AIS A impairment refers to a patient with no motor or sensory function in the relevant segments at and below the injury, and is considered to be complete paralysis.
All patients in the trial received six injections in, or around, the injury site, using the same cells and similar procedure (with Neuralstem’s proprietary Spinal Cord Delivery Platform and Floating Cannula) as the company’s ALS trials. All patients are receiving physical therapy post-surgery to guide newly formed nerves to their proper connections and functionality. The patients also received immunosuppressive therapy, for three months, as tolerated.
The primary objective of the Phase I trial, which commenced in September 2014, is to determine the safety and toxicity of human spinal stem cell transplantation for the treatment of paralysis and related symptoms due to cSCI. The secondary objectives of the study are to evaluate graft survival in the transplant site by MRI, as well as the effectiveness of transient immunosuppression. Additionally, the study will look at exploratory objectives to evaluate the ability of NSI-566 transplantation to positively affect AIS level, ISNC SCI motor and sensory index scores, bowel and bladder function, pain, UAB IMR scores, SCIM scores, evoked sensory and motor potentials, and electromyogram (EMG).
An NSI-566/acute spinal cord injury Phase I/II trial is awaiting IND approval in Seoul, South Korea. CJ CheilJedang has an exclusive option agreement for cell therapy products in South Korea and five additional South Asian countries.
For more information on the trial:
For more information on spinal cord injury: