Spinal Cord Injury Research: Overview
Spinal cord injury (SCI) research is the primary emphasis of the Center. Throughout the years, we have pursued various technologies to ameliorate the consequences of damaged cord tissue. Several have gone through FDA Phase 1 trials and are in the commercialization process. These therapies can be subdivided into several tracks:
Neuroprotection from Secondary Injury: Primary injury is the defined as the initial mechanical/thermal trauma to the cord. This process is irreversible. Primary injury induces cell death, which can in turn, lead to the release of biochemical toxins outside of the cell. These toxins subsequently negatively affect neighboring healthy cells (bystander damage), which feeds into a positive feedback loop of exacerbating the initial insult. The seminal event in initiating secondary injury is damage to the cell membrane. Thus, a key theme in our research is to “seal” these breaches in the cell membrane, thereby rescuing cells from certain death. Other therapeutics include scavenging the toxins that are produced as a consequence of damage.
Restoring Lost Function:
In certain instances of spinal cord damage arising from mechanical insult or disease (such as multiple sclerosis), the nerve fibers remain intact, but the myelin sheath is disrupted. This perturbation or delamination of the myelin sheath exposes ion channels that are normally silent. The end result is conduction block. Over the years, our Center has developed novel potassium ion channel antagonists that block these exposed ion channels, thereby restoring conduction to dysfunctional nerve fibers. Such agents have received FDA approval for treating symptoms associated with multiple sclerosis.
Regeneration of the Spinal Cord:
Paralysis is predominately a white matter disease and these damaged tracts prevent the conduction of action potentials that ascend/descend the cord. Traditionally, the injured spinal cord microenvironment has been thought of as non-permissive to regeneration, but our Center is looking into ways to convert this inhibition to promote regeneration of nerve fibers across the lesion. Two approaches under investigation are the modulation of the immune response and the use of DC electric fields to stimulate nerve fiber growth. The latter technology has gone through both veterinary and FDA Phase 1 trials. Currently, the Center is looking for collaborations for additional veterinary and human clinical trials. For more information regarding previous trials and new iteration of the technology, see below:
*Note: The Center is looking for veterinary and human clinical collaborators to help assess the next generation of spinal cord stimulators.
- Polyethylene glycol (PEG), has undergone FDA Phase 1 trials
- Chitosan and silica based nanoparticles/nanoconjugates
- Targeting and neutralization of reactive oxygen species, reactive nitrogen species and aldehydes
- 4-AP and derivatives (commercialized as FDA approved AMPYRA, to improve walking speed in multiple sclerosis patients)
- Modulation of the immune response post-SCI.
- Use of low level DC electric fields to encourage regeneration (undergone FDA Phase 1 trials).