Traumatic spinal cord injury (SCI) is a devastating and sadly not uncommon injury suffered on the battlefield. Although protective wear provides a sufficient deterrent to projectiles and shrapnel for regions of limited mobility such as the chest, the neck and face are often exposed, thus leaving the soldier prone to spinal cord and brain injury. Life-long complications of SCI account for large costs of Veteran care, strain families, and are associated with depression and reduced ability to reintegrate into civilian life. With a dearth of therapies available for either acute or chronic SCI in the clinic let alone on the battlefield, the development and translation of strategies to repair the injured CNS are urgently needed to restore function after SCI. Cell therapies offer the promise of being able to provide a means of neural tissue and functional replacement; they can provide a broad range of beneficial actions due to the intricate complexities and functionality of a cell compared to a single biological or pharmacological agent.
The usefulness of one particular type of cell, the Schwann cell (SC), for human transplantation is supported by extensive preclinical data. SCs are critical to providing regeneration and restoration of function following injury to nerves of the legs or arms. SCs have been demonstrated in a large body of scientific work to be effective in promoting axon growth, remyelination, and functional recovery in a variety of experimental spinal cord injury (SCI) models (contusion, compression, transection) to different levels of the spinal cord (cervical and thoracic) in both acute and chronic stages of injury. No other cell type employed in SCI has the breadth of supportive experimental data for their utility in repair. Importantly, tens of millions of human SCs can be derived for autologous (self) implantation after a simple surgery for harvesting a small piece of nerve from an injured person's leg, and the subsequent expansion and purification of the cells in culture, obviating the need for immune suppression as is the case with most other cell therapies, particularly stem cell-based treatments. SCs may also serve as an important component of future combinatorial therapies. SCs have been demonstrated to provide greater anatomical and functional efficacy when genetically modified, combined with pharmacological or biological agents or used in conjunction with biomaterial platforms.
The proposed studies will be conducted to generate important pre-clinical data for submission of an Investigational New Drug (IND) application to request permission from the Food and Drug Administration (FDA) to initiate a Phase 1 safety study using autologous human SCs for ASIA A acute (within 24 hours of injury, 5 individuals) and ASIA B chronic (at least 2 years post-injury with a stable functional baseline, 5 individuals) patients. The SCs will be derived from the patient's own peripheral (sural) nerve, purified and expanded in culture over a 2 to 4 week period before spinal cord implantation. The proposed experiments are designed to identify the optimal cell dose to employ, to demonstrate the long-term persistence and limited CNS distribution of SCs after implantation and to show that SC implantation is not accompanied by various adverse, toxic or painful effects. We have already initiated the pre-IND process through communications with the FDA, who have provided critical feedback on the design and implementation of the pre-clinical experiments proposed. Therefore, the completion of these studies will complete the pre-clinical data set required for our IND submission. The other two pieces of our IND submission are almost ready; we have the procedures and facilities in place to generate the clinical grade product and have written the clinical protocol.
By targeting both acute and chronic SCI patient populations we hope to develop a therapy that can be used in the majority of persons with spinal cord trauma. Our timeline for moving forward will be to submit the IND upon obtaining positive indications from the three preclinical arms of this investigation and begin enrolling patients for the Phase 1 clinical trial and the establishment of pre-treatment functional baselines (chronic wing). The proposed cell therapeutic has 15 years of preclinical experimental research behind it and we have assembled a team of outstanding scientists and clinicians to bring this exciting treatment to fruition as one of the first cell therapies for repair of the injured nervous system.