ARRA Investments in Spinal Cord Injury
Public Health Burden
More than 200,000 people in the U.S. live with a disability caused by spinal cord injury, and about 11,000 new injuries occur each year. Although spinal cord injury can occur at any age, many young people are affected and face a lifetime of disability and suffering, often with loss of independence and extraordinarily high economic costs.
Acute treatment and prevention of secondary damage
Damage to nerve cells and fibers and to supporting cells within the spinal cord continues to progress for several days, perhaps even weeks, following a traumatic injury. NIH supports many grants that aim to understand the cascading mechanisms responsible for this secondary damage and to develop interventions that protect the spinal cord and maximize recovery. Examples of ARRA funded grants include:
An exploratory grant is developing a new technology (using “hydrogels’) to provide sustained release of drugs into the spinal cord that can reduce the secondary damage that continues for many hours after an injury.
A research grant is identifying therapies to protect blood vessel cells in the spinal cord following trauma. Blood vessel cells are often the first cells to die, triggering further damage to nerve cells.
Scientists are studying matrix metalloproteinases (MMPs), a group of proteins that contribute to both damage and tissue repair following spinal cord injury. The goal is to develop therapies that block the harmful actions of MMPs without compromising their desirable effects.
Treating the consequences of spinal cord injury
Because of improved care, people are far more likely to survive a spinal cord injury than in the past. However, spinal cord injury causes partial or complete loss of voluntary movement and sensation, with the extent depending on the degree of damage and the level at which the spinal cord is injured. People with spinal cord injuries also confront chronic pain, loss of bowel and bladder control, pressure sores, and increased susceptibility to respiratory and heart problems, which can be life threatening. Examples of ARRA grants addressing these issues include:
A Challenge grant is developing and testing in animal models a novel stem cell transplantation strategy to treat bladder dysfunction and involuntary muscle spasms, which are a major health problem for people with spinal cord injuries.
Another Challenge grant is evaluating a minimally invasive method to activate muscles electrically to restore cough in people with spinal cord injuries. This could reduce potentially life threatening respiratory complications and improve quality of life.
An exploratory grant is testing a novel approach to restoring respiratory function after spinal cord injury in animals. The therapy is based on new understanding of drug induced plasticity in the nerve cell circuits that control respiration.
A new research grant is studying how the drugs that treat spasticity enhance or interfere with voluntary movement control in people with incomplete spinal cord injuries. The findings will have important implications for therapies aimed at maximizing function.
Regeneration and Repair
The brain and spinal cord do not repair themselves following damage. Research is revealing the factors that block regeneration and restoration of function to overcome these barriers and encourage the latent capacity of the spinal cord to recover. Examples of ARRA funded projects in this area include:
A new research grant is developing therapies to repair spinal roots using natural “neurotrophic” (nerve cell growth and survival promoting) substances. Spinal roots, which connect nerves of the body to the spinal cord, are often damaged in vehicle accidents or falls, resulting in life-long disability.
Scientists are studying how molecules called extracellular proteases promote regeneration and functional recovery following spinal cord injury. Understanding proteases may lead to therapies that promote formation of new nerve cell connections to restore lost function.
Research focused on the molecules that retard growth of nerve fibers in the damaged brain and spinal cord aims to develop interventions that overcome these factors and encourage growth and recovery following injury.
A new research grant is promoting nerve fiber regeneration and functional recovery after spinal cord injury in mice by manipulating a protein called mTOR, which recent studies implicate as a regulator of axon growth.
A GO grant is studying the amazing ability of the axolotl (Mexican salamander) to regenerate following damage to the brain and spinal cord. The goal is to identify targets for interventions to encourage regeneration and recovery in people following brain and spinal trauma.
A major supplement to an ongoing research grant will enable researchers to accelerate promising studies to repair white matter loss following spinal cord injury, which contributes to functional problems. The experiments in mice use a growth factor to encourage the spinal cord to generate new glial (supporting) cells, which make up white matter, following spinal cord injury.
-- Development of Biomaterials that Release Therapeutic Agents to Modulate Inflammation -- Gilbert, Ryan J. (MI)
-- Vascular responses as therapeutic targets after SCI -- Hagg, Theo (contact); Whittemore, Scott (KY)
-- Matrix Metalloproteinases and Spinal Cord Injury -- Noble, Linda J. (CA)
-- Spinal cord injury: Targeting local inhibition to improve outcome --Kriegstein, Arnold (contact); Noble, Linda J. (CA)
-- Evaluation of Wire Electrodes to Activate the Expiratory Muscles to Restore Cough -- Dimarco, Anthony F. (OH)
-- Molecular Mechanisms Mediating Recovery after SCI-Induced Hemidiaphragmatic Paralysis -- Nantwi, Kwaku Daniel (MI)
-- Reflex Regulation of Motor function in Human SCI -- Schmit, Brian D. (contact); Hornby, Thomas George (IL)
-- Repair of Brachial Sensory Root Injuries in the Spinal Cord -- Frank, Eric (MA)
-- Proteases in Spinal Cord Plasticity & Regeneration -- Seeds, Nicholas W. (CO)
-- Molecular Determinants of Adult CNS Axonal Growth -- Strittmatter, Stephen M. (CT)
-- Promoting axon regneration and functional recovery after spinal cord injury -- He, Zhigang (MA)
-- Validation of a Novel Genetic Model for Neural Regeneration -- Scott, Edward W. (FL)
-- Cellular Interactions in Spinal Cord Contusion -- Wrathall, Jean R. (DC)
Page Last Updated on June 30, 2018
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