To cure the paralysis and loss of function that spinal cord injuries cause, doctors will need a series of carefully orchestrated interventions. Treatments are likely to start in the field, even before someone reaches the Emergency Room; continue for months; and include rigorous new forms of rehabilitation.
To speed the day when this therapeutic package is available, the Christopher & Dana Reeve Foundation supports research on a variety of fronts. Our largest, most comprehensive research initiative is the Individual Grants Program. Winners of these two-year grants comprise a multi-disciplinary cadre of researchers dedicated to solving the complex medical problems that result from spinal cord injuries, in both the acute and chronic stages. In addition, scientists and clinicians increasingly are turning their attention to biomedical devices and new forms of rehabilitation that already are restoring some measure of independence to people with severe spinal cord injuries.
Since 1982, the Reeve Foundation has awarded more than $103 million to over 650 researchers around the world. Their work falls into these major areas: Neuroprotection ; Promotion of Axon Growth and Remyelination; Axon Guidance, Synapse Formation, and Neurotransmission; Growth Inhibition; Cellular Replacement, Therapeutic Cells and Substrates; Stem Cells; Rehabilitation; Pain and Other Complications of Spinal Cord Injuries; New Tools and Models for Spinal Cord Research.
Neuroprotection. For weeks and possibly months after a spinal cord injury, the cellular casualty count continues to rise. The body's immune responses, the chemicals spewed by dying cells, and other natural processes triggered by an injury damage the cells that survived the initial trauma and cause others to self-destruct. The mayhem amplifies the size of the lesion and the loss of function. If this biological ripple effect could be prevented or contained, the injury might wreak less havoc.
Read more about apoptosis, the cellular suicide mechanism that a spinal cord injury activates.
Axon Growth and Remyelination. Spinal cord injuries destroy axons, but the neurons to which they belonged often are spared. Unfortunately, these neurons do not simply send out new axons nor repair the damaged ones. Some investigators are trying to "convince" neurons to do just that. One strategy is to reboot the development program in neurons so that they grow new axons that then could recreate the nerve circuits that an injury disrupts. Other researchers are exploring how the peripheral nervous system in the arms and legs repairs nerve damage, hoping that the process could be mimicked in the spinal cord. Another challenge is posed by spinal axons that survive the injury but then shed their protective wrap of myelin, which had enabled them to transmit signals. Researchers are closing in on a therapy that would remyelinate these stripped axons and also might reverse the demyelinating disease multiple sclerosis. A remyelination strategy also would ensure that if neurons could be coaxed to regrow their axons after an injury, they would have a proper myelin sheath.
Read more about axonal growth and demyelination.
Growth Inhibition. Unlike cells in the peripheral nervous system, cells in the central nervous system do not repair themselves after an injury. However, researchers now believe that spinal neurons might put out new axons were it not for the body's natural responses to a trauma, including inflammation. Those reactions transform the area around the lesion into hostile territory for axon regeneration. In addition, the myelin sheath, which normally insulates axons and enables them to transmit nerve impulses, also contains proteins that prevent neurons from regenerating their axons after a spinal cord injury. One day treatments will be developed that will stymie growth-inhibiting molecules or prevent them from congregating at the injury site so that the body can repair lost spinal-cord circuitry. Another strategy involves either protecting new axons from the toxic environment or bolstering them so they can muscle through it. Scientists also are beginning to explore mechanisms inside neurons themselves that interfere with axon regrowth and present new targets for therapy.
Axon Guidance, Synapse Formation, and Neurotransmission. Spinal cord researchers have had increasing success persuading neurons to regenerate their damaged axons following a spinal cord injury. However, in order to rebuild nerve circuitry and restore lost function, those newborn axons must travel distances up to several feet, recognize their target neurons, and forge working connections — or synapses — with them. In addition, the full complement of neurotransmitters, the chemicals that improve neuron-to-neuron communication, and their receptors also must be restored. Toward that end, an increasing number of researchers are focusing on how the brain and spinal cord are assembled in developing organisms. They study how certain guidance molecules keep elongating axons on track and how the growing tip of the axon receives information and nourishment during the journey. If this formative process could be restarted in the adult, then doctors would have a valuable tool for repairing the injured spinal cord. To help people recover function, scientists also are testing ways to exploit and strengthen the connections between the brain and spinal cord that survive most injuries.
Read more about synapses and neurotransmission.
Cellular Replacement, Therapeutic Cells and Substrates. One approach to spinal cord repair involves the replacement of neurons and their cadre of support cells that are destroyed or damaged by the injury and its aftermath. Toward that end, some scientists are trying to generate dependable lines of stem cells that, when transplanted, would evolve into the cell types needed to fix the injured cord. [See Stem Cells below.] Other researchers are experimenting with different types of transplanted cells and tiny guidance channels, which would provide the scaffolding, or substrate, to support new axons and keep them on track as they grow across a breach in the spinal cord. Both the cells and the tiny devices can be engineered to deliver substances that would promote the regenerative process and protect surviving cells. Peripheral nerve transplants also have shown promise as a way to patch nerve circuits. Another approach involves restarting the mechanisms that first created the nervous system.
Read more about spinal cord cells - neurons, astrocytes, microglia, and oligodendrocytes - and the challenges of central nervous system repair following an injury.
Stem Cell Research. Stem cells hold promise for treating a host of diseases and injuries. The most primitive of these cells, embryonic stem cells, give rise to all the different types of tissues in the body. Higher order stem cells known as neuroprogenitor cells spin off the all the cells that become the brain and spinal cord. If researchers can learn how to control the parent cells and the fate of their offspring, then stem cells might one day repair a damaged spinal cord. All types of stem cells are self-renewing in the body and in the laboratory, so large quantities might be grown for medical purposes. Pools of neuroprogenitors also appear to lie dormant in the recesses of the brain and spinal cord that might be roused and dispatched to the site of an injury. Researchers are working on understanding the basic biological mechanisms of stem cells with the hope that they might one day restore function to people with spinal cord injury.
Read about stem cells, the potential of stem cell research, our position on stem cells, and the latest stem cell research.
Pain and Other Complications of Spinal cord Injury. In addition to robbing people of mobility, spinal cord injuries also impair their control over bowel, bladder, and sexual function. Moreover, spinal cord injuries often spawn a range of medical problems, some life threatening. These complications include infection, spasticity, pressure sores, and dangerous irregularities in blood pressure and body temperature. And, tragically, two thirds of people with spinal cord injury suffer chronic, intractable pain after their injury, and a third of those rate that pain as severe. The Reeve Foundation encourages scientists to focus on these serious problems that compromise both the health and the quality of life of people who suffer spinal cord injuries and their caretakers.
Rehabilitation. Rehabilitation therapy helps to maintain bone and muscle mass and is vital for the general health of people with spinal cord injuries. Evidence is mounting that certain forms of rehabilitation also promote beneficial changes in the spinal cord itself and markedly improve function. For example, new training regimens based on repetitive treadmill stepping and gradually increased weight bearing may actually promote axon regeneration and "teach" the spinal cord below the injury to activate the muscles needed for walking and standing. The Reeve Foundation supports both laboratory and clinical research devoted to testing and perfecting new approaches to rehabilitation and to exploring the links between them and beneficial changes in the damaged cord and improvements in the health and functioning of people with spinal cord injuries.
New Tools and Models for Spinal Cord Research. To find effective treatments for spinal cord injuries, researchers must understand the exact course, over both time and distance, of the biological tempest that the injury spawns. Moreover, they must thoroughly test promising treatments in animal models of different types of injuries. The Reeve Foundation encourages the creation and use of new technologies and devices that will aid spinal cord research as well as the development of sophisticated models of spinal cord injuries.
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