Research Strategies To Find New Treatments For Spinal Cord Injury -- Experimental Drugs

An excerpt from an article in The Spinal Cord Injury Newsletter, Fall 1995

by Cheryl M. Chanaud, Ph.D.

Copyright ©1995 by Medical News Publishing, P.O. Box 99702, San Diego, CA 92169

Current treatments of spinal cord injury include modern surgical and therapeutic techniques that were unavailable 20 or 50 years ago. Yet, it was not until a mere five years ago that scientists successfully developed a treatment that directly treated the injured nervous system itself. This, of course, was the discovery that the drug methylprednisolone may reduce paralysis if given in the right dosage and with the right timing. Now we are also taking a serious look at tirilazad mesylate.

Among the many research strategies developed by scientists to encourage nerve tissue to heal is the primary strategy of using a chemical or pharmaceutical approach. A drug (chemical) is injected into the bloodstream. The drug travels to the site of injury; certain chemical interactions occur that help damaged nerve cells survive the injury. This may result in less paralysis.

Goals of Drug Treatments of Acute SCI

What are the goals of these drug treatments of acute SCI? Three primary goals are:

1. to preserve damaged nerve cells

2. to reduce tissue damage and bleeding

3. to encourage recovery of function.

What happens when the spinal cord is injured?

If we look at what happens during the initial stages of acute spinal cord injury, we can better understand the research strategy of using drug treatments. Upon initial traumatic injury, damage occurs to individual nerve cells in the spinal cord. Different parts of the nerve cell may be damaged; the cell body may break open or the parts of the cell that connect to other nerve cells may be cut apart. When a cell breaks open, the chemical contents from inside the cell can escape to the outside, and the chemicals that were outside, can now get inside. Depending on how badly the cell is damaged, it may die, it may survive and function partially, or it may survive and fully recover its previous functioning. Of course, successful drug treatments must help damaged nerve cells survive and recover their useful functions.

Secondary Injury

If we pull back from our narrow focus on an individual nerve cell in the spinal cord and look at the whole site of the injury, we find that many other things are also happening. Besides the structural damage to the nerve cell, there is structural damage to the vascular tissues, that is, the tissues providing blood to the nerve cells. The mechanical damage to the capillaries, arteries, and veins results in bleeding at the site of injury. This loss of blood means that nerve cells are not receiving the oxygen and nutrients that are necessary for normal functioning. Thus, even if a cell is not damaged directly by the traumatic injury to the spinal cord, it may be injured secondarily by having its blood supply reduced or cut off.

This sequence of events leads to significant changes in the chemical environment of all cells near the site of injury. In the past several years, new research has identified some of the many naturally occurring chemical changes that drastically alter the local neural environment. These include: excess calcium entry into cells, drastic decrease in blood flow, production of chemicals in amounts that can cause damage, decreases in oxygen, swelling, and many others. Scientists refer to these detrimental changes as post-traumatic secondary damage.

Scientists believe that methylprednisolone (now a standard treatment for acute SCI) and GM-1 Ganglioside (still an experimental treatment for acute SCI) may have their beneficial affects by reducing secondary damage.

Research Strategies to Combat Secondary Injury

Pharmacologic approaches are among the most promising research strategies to treat the neurologic damage caused by acute SCI. Each micro-stage in the process of secondary damage is an opportunity for intervention and possible treatment. Current experimental drug approaches are focusing on three main strategies:

1) stabilizing the levels of calcium ions,

2) reducing the production of molecules called 'radicals', and

3) inhibiting a group of molecules known as 'excitatory amino acids'.

Many drugs are currently under consideration for possible use in experimental treatments, in animals or humans, to treat secondary damage. During an interview of an eminent SCI researcher, Dr. Wise Young, he was asked what he believes are the most promising experimental drugs to treat acute SCI. Dr. Young responded, "Several drugs have been shown to be effective in animal models of spinal cord injury. The most promising of these drugs include tirilazad mesylate, YM14673, nalmefene, CNQX and mianserin. These drugs are being systematically assessed. They will be tested individually and in combination with methylprednisolone. The goal is to identify the best new therapy that should be tested in the next human clinical trials." Researchers are very hopeful that one or more of these drugs will prove to be more effective than methylprednisolone and, hopefully, bring about greater levels of functional recovery after traumatic SCI.

Return to CPN Home Page