What are the prospects for “curing” spinal cord injury, multiple sclerosis, and related injuries of the central nervous system?
By Lakshmi Bangalore, PhD
The spinal cord is the only bridge that connects the brain to a vast majority of the body. The cables of wire-like nerve fibers within the bridge provide the path for millions of electrical signals that exert the brain’s control on the many organs and organ-systems, allowing them to perform their respective functions.
When such a bridge is broken or damaged, there are important consequences. Paralysis, the inability to consciously move, is one of the most severe and devastating consequences. It is often accompanied by impaired control of bladder and bowel, as well as of vital functions such as blood pressure and respiration. There is also loss of sensation below the level of the lesion.
Another consequence of damage to the spinal cord, as paradoxical as it may seem, is pain, an often excruciating form of pain called neuropathic pain. There is currently no cure for these life-altering penalties of spinal cord injury (SCI). But, importantly, there is also no longer the weighty pessimism that was once associated with the prospects of fixing the broken spinal cord or the consequences thereof.
In fact, a cure, which once seemed impossible, is now seen by many scientists as an achievable goal. Here are some reasons why.
The Myelin Connection
Scientists now know that in many cases of closed SCI, including complete injuries where there is little or no function below the region of injury, paralysis is partly due to damage to the myelin insulation that surrounds nerve fibers rather than due to severance of the nerve fibers themselves. Without the protective insulation of myelin, damaged nerve fibers, like frayed electrical wires, are unable to transmit electrical signals, and behave as if they have been severed even though they are intact.
While re-growing severed nerve fibers and connecting them to their correct targets still remains an attractive goal and continues to be actively researched, scientists are exploring ways to repair and overcome myelin damage as a tractable approach to restoring function, at least in a large number of patients with SCI.
During the past few years, several studies have shown that surgical transplantation of myelin- forming cells, including stem cells, into the injured (demyelinated) spinal cord can have a significant benefit in experimental animals. Ongoing studies are carefully examining the risks and benefits of using each of the different myelin-forming cells, the ease of delivery of such cells into the injured spinal cord, and, their usefulness in promoting repair.
These studies, although effort- intensive and tedious, are laying the necessary ground work for safe experimentation in humans.
Molecular Revolution
The molecular revolution has accelerated the pace of discoveries in biomedical science. Many of the molecules associated with neuropathic pain, unknown to us just a few years ago, are now being discovered. Similarly, we now know much about the molecules that produce remissions in MS, which suggests that it may be possible, in fact, to induce remissions, similar to those that occur in MS, in people with SCI. The complex and dynamic molecular landscape of injured nerve fibers is beginning to be uncovered, and this is making the systematic analysis of pain cascades and remission machinery possible, however daunting it may be.
As scientists continue to chip away, molecule by molecule, and explore strategies to control the molecular switches that control the way nerve fibers transmit signals, effective therapies that can silence just the type of pain associated with nerve and SCI (while maintaining all other normal and essential pain sensations) or cause remissions in people with paralysis due to damaged myelin will be within reasonable reach.
Recent advances in the understanding of molecular mechanisms that unleash secondary damage of nerve fibers, long after the initial period of injury, have led to increased awareness of neuroprotection as well as to the active investigation of drugs and other novel cell-based approaches to preserve nerve fibers and protect neurological function. Discoveries of the molecular revolution have already caught the watchful attention of pharmaceutical and biotech companies eager to capitalize by bringing them to market.
Quantum Leap
There is much optimism, and in fact a sense of excitement now, about a cure for injuries of the spinal cord. This optimism partly arises from the above stated discoveries, and the great momentum that continues to drive scientific research. But is also is a result of recognition that we are making great progress, month by month, and by appreciation that medical research moves forward incrementally, via small steps, and does not necessarily require a fixit- all “eureka” discovery.
Recovery of movement of all five fingers or the ability to write (which requires the recovery of function in just a few spinal segments) would be an important improvement for a person with C-6 SCI. Recovery of the ability to take a few crude steps would give a person with paraplegic the freedom to transfer without assistance. Many with SCI, multiple sclerosis, and other forms of central nervous system injuries and disorders would readily agree that effective relief from neuropathic pain without having to endure the serious side-effects of present day treatments; return of sensation, however small, to feel the comforting touch of a loved one; regained ability to control bowel and bladder movement, naturally and at will, each amounts to a cure in its own right.
While it is impossible to predict with certainty when these cures will come to fruition, they are now on the table as realistic goals. It is important to remember that only a few decades ago, restoring function to the injured spinal cord would have seemed like science fiction. Today, there has been a quantum leap from that thinking. Scientific advances of yesterday are making it possible today for us to realistically think about and work toward the cures of tomorrow.
Lakshmi Bangalore, PhD is the scientific liaison officer at the Center for Neuroscience and Regeneration Research, a collaboration of the Paralyzed Veterans of America and United Spinal Association with Yale University.
