Abstract
Primary spinal cord injury is followed by secondary, biochemical, immunological, cellular changes in the injured cord
A review article written by Brian Kwon looking critically at the use of hypothermia for SCI. It shows that it is neuroprotective in some settings (i.e. cardiac arrest). However, there are 25 animal studies with mixed results and only eight human SCI studies. Importantly, they are all case series of local, not systemic hypothermia. And the last one published was in 1984.
Rho is a critical molecule in SCI. Rho ultimately inhibits axonal growth cone proliferation. Stopping RHO therefore will promote the growth cone. There are two drugs that ultimately targets rho. These are anti nogo antibodies and cethrin both of which ultimately inhibit rho.
President Obama lifted the ban on federal funding of stem cell research. This was a monumental occasion and was right around the time that the FDA approved the first trial of hESC for SCI.
The FDA trial of Geron is with Thoracic ASIA A SCI patients with transplantation of ESC directly into the cord at 7 to 14 days after injury. Geron has provided evidence to the FDA that there is no teratoma formation with transplantation of a human ESC to a rat or mouse. However, we do not know what will happen in a human to human transplant.
In conclusion, use of steroids in setting of SCI is diminishing. There is no clinical evidence to support use of systemic hypothermia. Current clinical trials of pharmacologic therapy include Minocycline and RILUTEK(r) (riluzole) for neuroprotection, Anti-Nogo Antibodies and Cethrin(r) for axonal growth by ultimately inhibiting Rho. There is only one small study supporting safety, not efficacy of OEC transplantation.
