Neuralstem Cell Therapy
for Spinal Cord Injury
- Product status:
- U.S.: UCSD patient recruitment underway for FDA approved NSI-566/cSCI Phase I Safety Clinical Trial; FDA amended protocol to four patients total; Phase I commencement expected 2014
- South Korea: Korean FDA IND approval for NSI-566/Acute SCI Phase I/II trial expected in 2014; trial expected to commence in 2014 or early 2015
- 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 has received FDA approval to initiate a Phase I safety trial of its NSI-566 neural stem cells for chronic spinal cord injury (cSCI). This trial, also approved by the Institutional Review Board of the University of California, San Diego, School of Medicine, will enroll four cSCI patients with thoracic spinal cord injuries (T2-T12), who 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. The FDA amended the Phase I trial protocol to a total of four patients, due to the safety of both the cells and procedure, proven in Neuralstem’s NSI-566/ALS trials.
The primary objective of the trial, expected to commence in 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).
All patients in the trial will receive six injections in, or around, the injury site, using the same cells and procedure (with Neuralstem’s proprietary Spinal Cord Delivery Platform and Floating Cannula) as the company’s ALS trial. All patients will also receive physical therapy post-surgery to guide newly formed nerves to their proper connections and functionality. The patients will also receive immunosuppressive therapy, which will be for three months, as tolerated. The trial study period will end six months post-surgery for each patient, with a one-year Phase I completion goal.
An NSI-566/acute spinal cord injury Phase I/II trial is expected to commence in 2014 or early 2015 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:
- Principal Investigator’s Office, UCSD: (619) 471-0798
For more information on spinal cord injury: