Clinical Trials within U.S.: Spinal Cord Injury

WITHIN THE UNITED States, no clinical trials using stem cells for the treatment of spinal cord injury have been approved. This is not altogether surprising, as the field of stem cell research is still in its youth. With that said, there are several promising projects that are preparing to enter the clinical study phase.

Physiologically speaking, spinal cord trauma differs from other types of central nervous system injuries. Instead of cell bodies (as in the brain), the spine is predominantly composed of long axon tracts. As such, spinal cord damage results in loss of sensory, motor, or autonomie function. More specifically, damage to the spinal cord prevents transmission of sensory information to the brain, as well as transmission of motor and autonomie commands from the brain to the body. Effectively, areas below the level of injury lose sensation and control, which manifests as numbness and paralysis. Full loss of sensation and control is considered a “complete” spinal cord injury, whereas partial loss of function is “incomplete.” Characteristic of the central nervous system, neurons of the spinal cord have limited regenerative abilities, rendering most injuries permanent.

The advantage of damaging an axon is that it does not necessarily imply the death of its corresponding neuron. Rather, via a process known as Wallerian degeneration, only the severed portion of an axon is lost; the remaining, nucleus—containing segment remains viable, with the potential for regrowth. However, a cocktail of inhibitory biochemical signals produced by the microenviron—ment of the spine seems to be partially responsible for its limited regenerative properties. An associated process of Wallerian degeneration is the demyelination of damaged axons. This important component of neurons normally surrounds the axon tract to effectively serve as an electrical insulator. Through this mechanism, speeds of signal propagation through the axon can increase up to 70-fold. Without myelination, axons in the spine transmit information too slowly to support a functional human being.

Lest one believe that the full extent of spinal cord injuries arises only from the primary event, it should be noted that a secondary insult comes about from physiologic causes. Local invasion of inflammatory components and changes in vascular integrity results in fluid and cellular accumulation, which exacerbates cord compression. This added impingement on healthy tissue induces further destruction and demyelination. Following acute inflammation, a scar is formed at the lesion site, which creates yet another barrier against future growth. The incredible complexity of this process means that there are numerous points of possible intervention. From restoring myelin of injured neurons to creating a growth—facilitating microenvironment to stimulating neuronal [Page 131]regrowth, the sheer scope of the issue has required over a decade for studies to finally advance to the clinical trial phase.