GM-1 Ganglioside
Once again, the announcement of a new treatment approach has raised interest and hope in the SCI community. In a small study, the experimental drug Sygen®, or GM-1 Ganglioside, was given within 72 hours of injury and then continued for up to 32 days. Neurological assessments were conducted up to one year after the treatment. Individuals who received Sygen®showed significantly more Functional recovery than those who received a placebo.

Currently, a large scale multi-center clinical trial of GM-1 is ongoing with a targeted completion date of 1996-1997. In the current study, all patients receive the "standard" does of methylprednisolone. In earlier studies, a standard dose of methylprednisolone was not given.

There are two theories about how GM-1 Ganglioside may act on spinal cord tissue. The first is that it performs some type of damage control by reducing the toxicity of amino acids released after spinal cord tissue is injured. The "excitatory" amino acids cause cells to die and increase the damage caused by the initial injury. The second theory suggests there may be a neurotrophic effect, somehow encouraging the growth of injured neurons. Neither of these theories have been scientifically proven yet.

Sygen®has not yet been approved for clinical use in this country by the Food and Drug Administration (FDA). It has only been used in a limited number of experiments. Sygen®was provided recently to injured football player Dennis Byrd and approximately 65 other patients through an open-label protocol. Although this protocol is no longer in effect, the large double-blind, multi-center trial in acute SCI mentioned above is well underway.

Surgery
Clinical studies are being conducted by surgeons to determine the optimum time for surgery to relieve pressure on the spinal cord after spinal cord injury. Additionally, the use of delayed decompressive surgery is being investigated in cases of chronic SCI.

Preventing new injuries during spinal surgery
Intraoperative monitoring techniques have been developed to protect healthy nerve roots during spinal stabilization procedures. Scientists tested, first on animals then on humans, a technique that assists surgeons in the placement of metallic hardware for stabilization of the spine. The technique which utilizes nerve stimulation and muscle responses has been shown to effectively predict and allow the prevention of nerve damage during surgery in the lumbosacral spinal column.

Treatments for Chronic Spinal Cord Injury and its Complications

Functional Electrical Stimulation
FES uses implanted or external electrodes to stimulate paralyzed nerves so that arms and legs can be used for improved function. Over the past decade, three primary applications for FES have been developed: FES for exercise; FES for upper extremity (hand/arm) function; and FES for lower extremity (leg function.) FES is discussed in detail in Fact Sheet: Functional Electrical Stimulation: Clinical Applications.

Omentum Transposition
One controversial treatment for SCI is Omentum Transposition. The omentum is a band of tissue in the abdomen of mammals which provides circulation to the intestines.

A surgical procedure is used to partially detach the omentum, tunnel it under the skin and suture it in place at the injury site. The omentum tissue, which is rich in blood vessels, may supply the damaged nerve cells with vital oxygen. It is believed that the omentum tissue may also secrete chemicals that stimulate nerve growth, as well as have the ability to soak up fluids to reduce pressure which can damage nerve cells.

Initial animal trials seem to show some functional improvement if the operation is completed within 3 hours of injury. Little or no improvement is shown when the procedure is done 6-8 hours post injury. This research, however, has never been scientifically documented.

The on-going clinical trial for people who have had a SCI for months or years has recently been cancelled. Many scientists believe it is premature for human trials, since the results of the earlier research have not been sufficiently documented.

Biomedical engineering
Scientists in the field of biomedical engineering developed mechanical devices that use today's computer technology to assist individuals in activities of daily life. Examples of the types of devices under research and development are environmental control devices, electronic had grip device, and walking devices.

Spasticity/Pain
The complications of spasticity and pain are common in spinal cord injury. Spasticity that is severe enough to cause problems with mobility and self care, that contributes to Skin Breakdown, and that causes pain is reported in a number of cases of SCI.

Studies in the treatment of spasticity are investigating pharmacological agents, Intrathecal Baclofen, and spinal cord stimulation. In addition to drugs that have been available for some time (baclofen, valium, dantrium) the use of tizanidine has recently been explored. FDA approval of tizanidine is expected in late 1995.

The problem of pain occurs in approximately 50% of all cases of SCI. Five to thirty percent characterize the pain as disabling. Pharmacologic agents as well as surgical interventions such as the DREZ (Dorsal Root entry zone) procedure, cordotomy and cordectomy are under investigation for the treatment of severe causes of pain from SCI.

Male Fertility
In most SCI men, the ability to have an ejaculation and to father a child naturally is diminished. In fact, ten years ago, doctors were telling newly injured SCI men that they would not be able to father their own children. With advances made in procedures to assist men in obtaining an ejaculation as well as advances in assistive reproduction technology, SCI men now have the potential to become biological fathers. Vibratory stimulation and electroejaculation are procedures that have been investigated and are currently available to assist men in obtaining ejaculations.

Obtaining the ejaculation is only part of the fertility problem in SCI men, however, the semen from SCI men most often contains a lower than normal percent of motile sperm. Questions that researchers hope to be able to answer with investigations on the quality of sperm of SCI men are: what happens to semen quality following SCI? and how successful is artificial insemination and other reproductive technology using semen from SCI men?

Technology and research are making it possible for spinal cord injured men to consider options regarding their fertility and is providing a more encouraging answer to the question, "Will I be able to have children?" Additional Information is available in Factsheet: Male Reproductive Function after Spinal Cord Injury.

Alternative Therapies
Various controversial treatments for SCI have come and gone over the years, but none have proved to be effective in reversing the damage to the spinal cord that occurs in spinal cord injury. Often alternative therapies are very difficult to evaluate because of the unscientific nature in which the treatments are introduced to the human population. Many alternative therapies have no documented scientific evidence to substantiate their effectiveness. Currently, examples of treatments that fall into this category are the use of Sygen (GM-1) in chronic injuries and omentum transposition.

Summary of Treatment Research
Over the last several years there has been progress in the treatment of acute SCI to limit damage and preserve function. Treatment of chronic SCI presents a greater challenge, as damage that has already occurred must be corrected and then reversed.

It is entirely possible that, given appropriate financial support, many of the complex problems of SCI one day will be solved. Until that day arrives, it is import-ant to urge the federal government to provide broad-based support for basic science research so the fundamental questions about how and why the CNS acts the way it does can be answered. A cure or new treatments are possible only if scientists receive the support necessary to con-tinue their work in this important area.

• For further information on Freedox®clinical trials, contact: Upjohn Company, 929 Lawrence Court, N. Bellmore, NY 11710, 516-486-5276.
• For further information on Sygen®clinical trials, contact: Fidia Pharmaceutical Corp., 1401 I Street, NW, #900, Washington, DC 20005, 202-371-9898.
• For further information about FES applications, contact: the F.E.S. Information Center, 25100 Euclid Avenue, Suite 105, Cleveland, OH 44117, 800-666-2353.
• For further information about The Miami Project, contact: The Miami Project, 1600 Northwest 10th Avenue, R-48, Miami, FL 33136, 1-800-STAND-UP.

Suggested Reading:

Books
Maddox, Sam, (1992): The Quest for Cure: Restoration of Function After Spinal Cord Injury, Paralyzed Veterans of America, 801 18th Street, N.W., Washington, DC 20006.

U.S. Department of Health and Human Services, National Institutes of Health, The NINDS Research Program, (1989): Spinal Cord Injury, NIH-NINDS, Building 31A, Room 8A16, 9000 Rockville Pike, Bethesda, MD 20892.

Newsletters/Magazines
International Spinal Research Trust Newsletter, International Spinal Research Trust, Nicholas House - River Front, Effield, Middlesex, England.

Paraplegia: International Journal of the Spinal Cord, Churchill-Livingston of Edinbourough London, Subscription Manager, Journal Department, Longman Group, 4th Avenue, Harlow Essex CN19 SA, UK.

Paraplegia News, monthly research column, Paralyzed Veterans of America, 801 18th Street, NW, Washington, DC 20006.

Progress in Research and Walking Tomorrow, the American Paralysis Association, P.O. Box 187, Short Hills, NJ 07078.

SCI Life, National Spinal Cord Injury Association quarterly publication.

The Project: News from the Miami Project to Cure Paralysis, Miami Project, 1600 NW 10th Avenue, R-48, Miami, FL 33136.

Manuscripts/Articles
Neural Grafting, Repairing the Brain and Spinal Cord, New Developments in Neuroscience, Congress of the United States, Office of Technology Assessment. Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402-9325.

Bracken, M., (May, 1990): A Randomized Controlled Trial of Methylprednisolone or Naloxone in the Treatment of Acute SCI, The New England Journal of Medicine, 322(20) pp. 1405.

Bunge, R.P., et. al (1991) Regeneration of Axons from Human Retina In Vitro. Experimental Neurology, 112:243-251.

Bunge, R.P., et. al (1991) Isolation and Functional Characterization of Schwann Cells Derived from Adult Peripheral Nerve. Journal of Neuroscience. 11:2433-2442.

Bunge, R.P., et. al (1992) Sygeneic Schwann Cells Derived from Adult Nerves Seeded in Semipermeable Guidance Channels Enhance Peripheral Nerve Regeneration, The Journal of Neuroscience, 12(9): 3310-3320.

Bunge, R.P. (1994) Clinical implications of recent advances in neurotrauma research. In: The Neurobiology of Central Nervous System Trauma, (Salzman, S.K., Faden, A.I., Eds.). Oxford University Press, pp 329-339.

Calancie, Blair, et. al (1992). Intraoperative Evoked EMG Monitoring in an Animal Model, A New Technique for Evaluating Pedicle Screw Placement. Spine Vol 17, Nol. 10; 1229-1235.

Calancie, Blair, et. al, (1994). Involuntary stepping after spinal cord injury. Brain 117; 1143-1159.

Geisler, F.H. et. al., (June, 1991): Recovery of Motor Function After Spinal Cord Injury - A Randomized, Placebo-Controlled Trial with GM-1 Ganglioside, The New England Journal of Medicine, 324(26) 1829-1838.

Guenard, V., Xu, X.M., Bunge, M.B. (1993). The use of Schwann cells transplantation to foster central nervous system repair. Seminars in the Neurosciences 5;410-411.

Onifer, S.M., Whittemore, S.R., and Holets, V.R. (1993). Variable morphological differentiation of a raphe-derives neuronal cell line following transplantation in adult rat CNS. Experimental Neurology 122;130-142.

Travis, John, (October 1992): Spinal Cord Injuries: New Optimism Blooms for Developing Treatments, Science, Volume 258, pp 218-220.

This fact sheet was prepared with the assistance of Dr. Cheryl Chanaud of the National Institutes of Health and Dr. Naomi Kleitman and Marie Amador, RN, CRRN of the Miami Project to Cure Paralysis. This factsheet is offered as an information service and is not intended to cover all treatments nor research in the field, nor is it an endorsement of the methods mentioned herein. Any information you may have to offer to further update this factsheet would be greatly appreciated. The National Spinal Cord Injury Resource Center (NSCIRC) provides information and referral on any subject related to spinal cord injury. Contact the resource center at 1-800-962-9629.