Life on Wheels (77 page)

The following questions still remain about Schwann cells:

Can enough cells be placed and controlled to bring about optimal repair?

There are a number of different kinds of nerve tissues to be repaired in the spinal cord. Can Schwann cells affect them all?

Can Schwann cells penetrate to the areas of the cord where regeneration is needed?

At this stage, getting nerves to grow in the spinal cord is not really the problem. Now it is a matter of getting enough of them to grow long enough and establish functional connections. Dr. Young estimates that about 10% of connections are sufficient to support substantial functional recovery in rats and humans. Since most people still have some connections remaining across the injury site, regeneration only needs to make up the difference.

Regeneration of the spinal cord is not just a matter of giving someone a pill or an injection. Growth factors must be integrated into the complex, continuous metabolic processes in the body. Growth factors must get to the right place, interact with other very specific molecules, and be replenished as they are used. Rather than just putting growth factor into the body, researchers are finding ways of getting the body to produce the growth factor itself.

A University of California, San Diego, team is using fibroblasts. These are cells in the skin that can produce substances that affect nerve growth. Fibroblasts have certain advantages. As Wise Young explains:

Dr. Samuel Kuwada of the University of Michigan is performing a “molecular genetic analysis of axon guidance in the spinal cord.” Neurons make connections with their appropriate target cells by relying on specific molecules that direct axons. Scientists believe that identifying and understanding these guidance molecules may help direct regenerating axons to the right place. The University of Michigan researchers use zebrafish embryos to help them generate molecules called netrins. Netrins appear to play a role in making connections during embryonic spinal cord development.

Dr. Marc Tessier-Lavigne is also exploring netrins at the University of California, San Francisco. His team’s work suggests that a couple of different netrin molecules are found in the adult CNS. Their research abstract states:

Then again, maybe the exact nerve pathways don’t have to be recreated. Another avenue of research has studied exactly what the pathways are that produce the unique combination of impulses that make walking possible. There is some early evidence that the body has the capacity to reroute its messages, like a telephone operator plugging into a different line. The human body has some remarkable adaptive abilities, and part of the solution to the puzzle may involve letting the body do its own thing by simply removing the impediments and then giving it the building blocks it needs. These are known as pattern generation studies.

Walking apparently doesn’t rely entirely on messages from the brain. Part of the process of walking happens below the level of the injury— impulses traveling between muscles and the spinal cord without having to make it past the injury and back to the brain. It is not clear to what degree this might be the case in humans, but Miami Project researchers have studied a person with a 17-year history of incomplete cervical injury who began exhibiting involuntary stepping-like movements in his legs. This study strongly suggests that there is a “central pattern generator,” a group of nerve cells that synchronize muscle activity during alternating stepping of the legs.

This discovery—accelerated by Christopher Reeve’s demonstration that continued activity can result in restoration of sensory and motor function, even years after injury—has fostered an entirely new avenue of research and rehabilitation: activity-based therapy. Spearheaded by neurologist Dr. John McDonald—who worked directly with Reeve—at Washington University and The Rehabilitation Institute of St. Louis, physical therapy gyms are now commonly equipped with a treadmill over which an injured person can be suspended in order to simulate walking. Functional electric stimulation (FES) bikes are another means of simulating motion in the legs for this purpose.

In this way, the pattern generators are encouraged to get involved. According to McDonald, this process even fosters the regrowth of spinal cord axons, creating functional connections. Activity-based rehab is the most notable and exciting recent addition to the milieu of CNS research.

Recent computerized tools like CT (computed tomography) and MRI (magnetic resonance imaging) scans have fostered a revolution in medical care and research. SCI scientists are getting a highly detailed, three-dimensional look at the spinal cord thanks to these technologies.

Projects are underway that are designed to map the cord, including work at Purdue University and at Washington University in St. Louis, Missouri. At Purdue University, researchers are gathering information produced from 3-D images and making this material available as a database through computer networks that researchers can access. Dr. William Snider of Washington University believes that mapping the cord is critical to the process of achieving regeneration. He says:

A map of the spinal cord will also be a valuable diagnostic tool in the emergency room. The extent of injury will be much clearer to doctors, thanks to the ability to see a three-dimensional image of the injured cord.

Researchers also benefit from being able to better witness the effect of their therapies.

We’ve already discussed the need for lower motor neurons to be present for muscles to retain the ability for recovery in the case of a spinal cord regeneration. Research is also addressing the question of producing sufficient muscle mass for walking.

To determine whether muscle tissues could contract if the cord were repaired, physicians might perform certain simple diagnostic tests for the needed lower motor neuron activity. They would use reflex testing-tapping with that little hammer that we have all seen as a stereotype of a doctor’s checkup—or they might use an electrical stimulation device to see if muscles respond to a direct impulse. This would be evidence that muscle cells have not died and, so, would imply that lower motor neurons are in place.

If muscles are to be preserved and possibly restored in the future, at the time of injury, the lower motor neuron nerves need to be preserved or replaced before substantial muscle death occurs. According to Wise Young: “Neuronal replacement was considered science fiction until recently. The big discovery occurred rather quietly in the 1980s.”

You can accommodate a degree of motor neuron death. Explains Young:

In other words, there can be a degree of muscle cell death from lost gray matter in the spinal cord where motor neurons reside, and it can still be possible to build enough muscle strength for functional use.

Embryonic stem cells have become very familiar in American culture, the subject of a dramatic political and cultural debate about the ethics of using them for research and whether federal money should pay for such activities.

Here is the science. Cells from a human fetus or embryo have the ability to form themselves into any of the roughly 200 types of human cells. This type of cell is referred to as “pluripotent.” If we can harness and direct the capacity of stem cells to become any other kind of cell, then we can solve a huge range of medical conditions, not the least being regeneration of brain and spinal cord cells. People with Alzheimer’s disease, Parkinson’s, Huntington’s disease, diabetes, leukemia, epilepsy, and other conditions are believed to be in a position to gain from stem cell research as well. There have already been early successes with Parkinson’s disease.

When stem cells are inserted into another body, they are not seen as invaders, so rejection is less likely to occur. They integrate well with existing tissue. Several researchers have reported that they can induce these stem cells to differentiate into motor neurons. This suggests that it is possible to replace lost motor neurons in the spinal cord.

The missing growth factor needed for axonal growth is present in embryonic cells. These cells play a role in fetal development of the spinal cord, but “turn off” after we are born. Therefore, another avenue of research has been to transplant fetal cells directly into the spinal cord in the hope of switching back on the nerve growth capacity. Researchers choose embryonic cells rather than adult stem cells, which they do not believe have the same therapeutic potential.

Use of embryonic tissue is a delicate ethical and political issue. One of President Bill Clinton’s first acts of office in 1993 was to remove the fiveyear-old moratorium on embryonic cell research that had been imposed during the Reagan/Bush era. The only fetal cells that had been allowed to be used were those from spontaneous abortion (miscarriage). Spontaneous abortions are often the result of conditions that render the tissue unusable. Research is therefore limited to efforts in laboratories in the US that are able to find sufficient nonfederal funding and those outside of the US.

When President George W. Bush took office in 2000, one of his first acts was to strike federal support for embryonic stem cell research, limiting monies to only the “lines” that were already in existence—64 of them, as the public was told. Many researchers have stated that a small percentage of the 64 lines are actually of value in the laboratory.