Neural Regeneration Laboratory Program
The Neural Regeneration laboratory Program at Barrow is focused primarily on researching the potential of neural repair mechanism in following injury to the central nervous system. Special emphasis is placed on research studying the ability of the CNS to repair damage through the effects of exogenous growth factors, induction of endogeneous neural precursor populations, and direct precursor cell transplantation from non-embryonic sources (e.g., not of fetal origin).
Direct transplantation of stem cell precursors has been shown to result in beneficial therapeutic effects in animal models of spinal cord injury. This includes the use of precursor cells committed to developing along an oligodendroglial lineage. Experimental studies utilizing the application of recombinant Sonic Hedgehog (Shh) in models of rodent spinal cord injury have demonstrated proliferation of endogenous neural progenitor cells (reference 2, 3). Sonic Hedgehog is a molecule that is critically important in the development of the nervous system, particularly in the development of stem cells during embryogenesis. These cells have presumably arisen from a subpopulation of pluripotent cells lying dormant in the central nervous system of adult mammals and are induced to proliferate in the presence of Shh and spinal cord injury.
Models utilizing a demyelinating injury (similar to the injury to the white matter of the nervous system seen in Multiple Sclerosis, for example) in the dorsal column of adult rats have demonstrated increased numbers of progenitor cells in the grey and white matter of the spinal cord around the level of injury as well as around the central canal of the spinal cord (reference 1). In models of spinal cord contusion in adult rats, the addition of Shh to the site of injury has resulted in a strong trend toward improved functional recovery and axonal conduction when compared to control animals (reference 2, 3). The development of systemically administered Shh agonists allows study of the effects of chronic Shh activity within the nervous system following injury without requiring direct injection of the material into the spinal cord thereby avoiding the morbidity of such treatment (reference 3).
Ongoing work in the laboratory is focused on the ability of such agonists to stimulate stem cells to respond to the cellular environment after spinal cord injury and to enhance regeneration. It is hoped that this research will lead to therapeutic trials in which such agents may be administered to patients following spinal cord injury in order to improve their chances for recovery.
Acute Spinal Cord Injury Research
We have completed a Phase I/IIA clinical trial to investigate the potential of a new therapy, BA-210 (Cethrin®), in acute spinal cord injury. BA-210 is a recombinant protein thought to promote neuroregeneration and neuroprotection in the central nervous system (CNS) (reference 4). The first application of this medication in the world was at the Barrow Neurological Institute. As late as 2006, Barrow had the largest clinical experience with it in the world. Phase III human clinical trials are expected to begin soon.
Barrow researchers are also actively involved in numerous research protocols related to the imaging and cognitive functioning of patients with neurological injury.
References
The following website links are provided for your convenience only. These websites are independent of Catholic Healthcare West (CHW) and Barrow Neurological Institute. As such, Barrow and CHW do not endorse or sponsor any of these sites, nor do we vouch for the any of the information contained within these sites.
- Bambakidis NC, Wang RZ, Franic L, Miller RH. Sonic Hedgehog-induced neural precursor proliferation after adult rodent spinal cord injury. J Neurosurg (Spine) 2003;99:70-75.
- Bambakidis NC, Miller RH. Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion. Spine J 2004:16-26.
- Bambakidis NC, Theodore N, Nakaji P, Harvey A, Sonntag VKH, Preul MC, Miller RH. Endogenous stem cell proliferation after central nervous system injury: alternative therapeutic options. Neurosurg Focus 2005; 19(3).
- Alseres Pharmaceuticals website, http://www.alseres.com/product-pipeline/product-candidates/cethrin.asp. Accessed December 2007.
