Disease Focus Series: Spinal Cord Injury

The severe spinal cord injury sustained by Jockey Michael Martinez and the possibility (not realized) that he might be enrolled in Geron’s hESC-based spinal cord regenerative medicine trial, have drawn recent attention to spinal cord injury.

Christopher and Dana Reeve (see foundation here) as well as Don C. Reed (see site here) were instrumental in bringing attention to the significance of this injury and the importance of research to help patients with spinal cord injury.

More than 1 million Americans are living with a spinal cord injury. There are a variety of causes including car accidents, which are the most common cause. Other important causes include falls such as occurred to Martinez, the autoimmune disorders MS and also Traverse Myelitis that struck Cody Unser, sports injuries, cancer, and acts of violence (stabbing, gunshots).

The range of severity of effects from spinal cord injury vary with the location and intensity of the trauma (the higher in the spinal column generally the more severe the injury), but it frequently is profoundly devastating.

Thus, it is imperative that new, stem cell based treatments for spinal cord injury be developed. In order for this to happen, research into spinal cord injury and potential regenerative medicine treatments must proceed. At the same time there is great excitement about Geron’s ES cell based clinical trial moving forward now, the recent legal fight over the legality of ES cell research has thrown a chill over ES cell research that is the most promising for the future treatment of spinal cord injury.

The kind of treatment being pioneered by Hans Keirstead and Geron involves creating differentiated spinal cord cells such as oligodendrocytes (oligos), from human ES cells. The principle behind this approach is that the oligos will aid in healing of the spinal cord. Preclinical work has been extremely promising with treatment of paralyzed rodents leading to their being able to walk again.

An important element of this treatment, as highlighted by the recent case with Martinez, is that the injury has to be of a certain kind to be treatable using Geron’s approach. If too severe, the animal models would suggest the treatment won’t help. In addition, the treatment must be given with 1-2 weeks of the injury.

The NIH has a very interesting website on the history of spinal cord injury going back thousands of years.

What happens during an acute spinal cord injury and in the period following? (Of course during chronic injury such as from autoimmune disease, the temporal pathobiology is somewhat distinct.)

First, the actual injury physically damages the spinal cord including severing and demyelination of axons causing immediate loss of function.

Rapidly, the spinal cord begins to swell and there may be an influx of blood into the spinal cord that causes damage. However, typically the swelling then cuts off blood flow increasing the severity and extent of the damage due to lack of oxygen.

The spinal cord becomes inflammed as the body perceives the injury and mounts a major immune response that lasts days. There is some debate over whether this immune response could have some limited positive effects such as fighting off infection, but clearly  it does severe damage including causing the death of oligos. Hence, one objective of the Geron approach is to restore oligos, which can act as healers of the spinal cord and promote remyelination.

Another potential goal for stem cell-based regenerative medicine therapies would be to stimulate regeneration. One challenge with this possible approach is to encourage not only engraftment of a transplant but also appropriate, robust axon growth given the architecture of the spinal cord.

Finally, another key hope that stem cell research keeps alive is the development of treatments that could work beyond the first week or two after the injury.