Our approach to research
- A new era in spinal cord research
- Research we support
- Axon growth and remyelination
- Growth inhibition
- Axon guidance, synapse formation, and neurotransmission
- Cellular replacement, therapeutic cells and substrates
- Stem cell research
- Secondary dysfunctions of spinal cord injury
- Epidural stimulation
- New tools and models for spinal cord research
A new era in spinal cord research
There is so much promise in the field of spinal cord research as breakthroughs in science and technology start to translate into effective treatments for paralysis.
The Christopher & Dana Reeve Foundation has been leading the charge over the past 30 years by funding some of the earliest discoveries in basic science and supporting a pipeline of innovation across several fronts in the field.
Our mission is simple: drive innovation and invest in groundbreaking spinal cord research to advance promising solutions to the forefront of care.
Today, the Reeve Foundation supports an International Research Consortium on Spinal Cord Injury and two clinical research networks, the NeuroRecovery Network® (NRN) and the North American Clinical Trials Network® (NACTN).
Our newest initiative involves the use of epidural stimulation to promote functional recovery and improved health outcomes in individuals with chronic, complete spinal cord injury. The Reeve Foundation launched The Big Idea as a campaign to fast track the next phase of epidural stimulation research and expand the study to include additional participants.
Research we support
Doctors will need a series of carefully orchestrated interventions to cure the paralysis and secondary complications caused by spinal cord injury. Treatments are likely to start in the field, even before someone reaches the hospital emergency room, continue for months, and include rigorous new forms of rehabilitation.
Since 1982, the Reeve Foundation has awarded more than $120,000,000 to a vast network of researchers around the world.
The Reeve Foundation supports research on a variety of fronts, including these major areas:
For weeks and possibly months after a spinal cord injury, the cellular casualty count triggered by the initial trauma continues to rise. The body's immune responses – the chemicals produced 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 would likely wreak less havoc.
Axon growth and remyelination
Spinal cord injury destroys axons, but the neurons to which they belonged often are spared. Unfortunately, these neurons do not simply send out new axons or 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 could then recreate the nerve circuits disrupted by the injury. 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 lose their protective wrap of myelin, which enabled them to effectively transmit signals. Researchers are exploring interventions that would remyelinate these stripped axons, which in turn 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 and can effectively transmit signals.
Unlike cells in the peripheral nervous system, cells in the central nervous system (brain and spinal cord) do not spontaneously repair themselves after an injury. However, researchers now believe that spinal neurons might create new axons were it not for the body's natural responses to a trauma, including inflammation. Those reactions cause formation of a glial scar that transforms 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. Treatments are being developed to 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. Another area ripe for exploration is 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 experienced some 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. To 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.
Cellular replacement, therapeutic cells and substrates
One approach to spinal cord repair involves the replacement of neurons and their network of support cells that are destroyed or damaged by the injury and its aftermath. Researchers are trying to generate dependable lines of stem cells that, when transplanted, would evolve into the cell types needed to fix the injured cord. Others 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 channels can be engineered to promote the regenerative process and protect surviving cells. Peripheral nerve transplants also have shown promise as a way to patch nerve circuits.
Stem cell research
Regenerative medicine (the use of stem cells, both embryonic and adult, to treat injury and disease) is still in the early stages of exploration but holds enormous promise for individuals who live with a host of debilitating and life-threatening conditions. Embryonic stem cells are the most primitive of these cells and they give rise to all the different types of tissues in the body. Higher order stem cells, known as neuroprogenitors, spin off all the cells that make up 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 help to repair a damaged spinal cord. As scientists master the basic biological mechanisms of stem cells, it is hoped they will be able to drive these cells to a particular fate; direct them to become a specific type of cell or tissue and use them to treat afflictions like heart disease, diabetes, stroke and spinal cord injury.
Secondary dysfunctions of spinal cord injury
In addition to robbing people of mobility, spinal cord injury also impairs control of bowel, bladder, and sexual function. Moreover, the injury will often spawn a range of medical challenges, some life threatening. These complications include infection, spasticity, pressure sores, and dangerous irregularities in blood pressure and body temperature. 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 secondary consequences of a spinal cord injury can be extraordinarily debilitating, threatening an individual’s health and well-being on a daily basis. Scientists are closing in on a number of approaches to mitigate these potentially disastrous dysfunctions and in some cases, restore function.
Several decades of basic scientific research have led to the understanding that activity-based rehabilitation can help promote neurological recovery and improve overall function and health. Activity-based rehabilitation involves “interventions that target activation of the neuromuscular system below the level of the lesion, with the goal of retraining the nervous system to recover a specific motor task.” (Behrman et al, 2000) 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. It is now quite clear that rehabilitation is about much more than compensating for what has been lost. Scientific evidence underpins exciting new rehabilitation strategies designed to aid the repair process and promote improved functional and health outcomes after spinal cord injury.
Epidural stimulation is the application of a continuous electrical current, at varying frequencies and intensities, to specific locations on the lower part (lumbosacral) of the spinal cord. The initial research involved four young men, all with chronic, complete injuries, who were implanted with a stimulator at T11 - T12. All four were able to stand and voluntarily move their legs (with the stimulator turned on, they are able to flex their hips, ankles, toes and fully bear their own weight); later they each recovered varying degrees of bladder, bowel and sexual function and experienced improvements in their health (increased muscle mass, regulation of blood pressure and body temperature and an overall improved sense of well-being). Remarkably these autonomic recoveries persist even with the stimulator turned off. Now in The Big Idea, the Reeve Foundation will test epidural stimulation in a larger, more diverse group of 36 participants, all with chronic, complete injuries. The ultimate goal, presuming continued safety and efficacy are shown, is to bring epidural stimulation into the clinic as quickly as possible.
New tools and models for spinal cord research
To develop effective treatments for spinal cord injury, researchers must better understand how the uninjured cord works and the exact biological impact of the injury over both time and distance. Moreover, they must thoroughly test promising treatments in animal models of different types of injuries. Creating new technologies and devices to aid this research, and new, more sophisticated injury models, is critical to the success of our mission for safe and effective therapies for spinal cord injury.
We live in a time when the words 'impossible' and 'unsolvable' are no longer part of the scientific community's vocabulary. – Christopher Reeve
Thanks to the framework that the Reeve Foundation has set over the past three decades, the field of spinal cord research is overflowing with ideas and buzzing like a hive of innovation. It’s inspiring to see young scientists take on the challenge of curing spinal cord injury because they know we will advance effective treatments to the forefront of care in a matter of years, not decades.