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Rewarding Research

Reprinted from PN/Paraplegia News April 2014

The PVA Research Foundation is dedicated to supporting studies that can help make life better for veterans and others with SCI/D.

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Research into all aspects of spinal-cord injury/disease (SCI/D) is full of hope, far-reaching, ever-changing, always challenging and continually in need of support.

Paralyzed Veterans of America (PVA) is a leader in providing financial help and support for many SCI/D-related studies, including medical research, physical rehabilitation and everyday living, just to name a few. These studies not only help veterans, but everyone with SCI/D.

This year, the PVA Research Foundation has awarded just over $1 million in grants to people from across North America to look at everything from treatments for urinary tract complications to conflict resolution between people with SCI/D and their caregivers.

The PVA Research Foundation awards grants in four categories including basic science, design and development, clinical and fellowships.

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These are a brief descriptions of this year’s grant recipients.

Basic Science

Microglia Polarization Protects White Matter & Promotes Regeneration
David Stirling, PhD
University of Louisville Research Foundation
$150,000 (two years)

Spinal-cord injury (SCI) often destroys axons, a vital component of the body’s wiring that allows us to sense and move within our environment. Once axons are severed they’re unable to regenerate due, in part, to inhibitory cellular debris and scar formation.

Through this proposal we’ll investigate whether promoting an alternative activation state of microglia — the immune cells of the central nervous system —will provide a more permissive environment so axons can regenerate. We’ll accomplish this by using state-of-the-art microscopy that allows us to track microglia, other immune cells and axon growth after injury, as these dynamic changes occur after SCI. The information obtained may identify novel targets that stimulate microglial-mediated spinal cord repair.

Inosine: A New Treatment for Urinary Tract Complications following SCI
Rosalyn Adam, PhD
Boston Children’s Hospital
$150,000 (two years)

Spinal-cord injury (SCI) has devastating and often life-long effects on its victims and their caregivers.

Due to the risks associated with military training and service, military personnel are at greater risk of SCI than others. A major complication resulting from SCI is the loss of bladder control, which is associated with physical, economic and psychological distress.

In recent studies, we’ve identified significant improvements in bladder function in spinal-cord injured rats that are given a substance called inosine. A daily dose of inosine was able to significantly reduce the abnormal overactivity of the bladder that results from SCI.

The goal of our study is to investigate how inosine improves bladder control and to determine the treatment regimen that best improves bladder function. Successful completion of the study would provide the basis for translating this approach to human patients with SCI.

Clinical

Conflict Resolution Training for Reducing Caregiver Burden & Stress
Peter Hunt, PhD, MPH
Southern California Institute for Research and Education
$75,000 (one year)

Caregivers for veterans with spinal-cord injury (SCI) face insurmountable challenges every day.

This can result in high levels of caregiving burden and stress and lead to potential emotional conflicts between caregivers and care recipients. Conflict resolution is a skill set that can be used to promote effective solutions among conflicting parties. Providing caregivers with appropriate conflict resolution training may have the potential to lessen caregiving burden and stress.

This project has two main objectives: 1. To determine if the root causes of conflict arise in caregiving settings by conducting focus group discussions with caregivers and veterans with SCI; and 2. To develop a conflict resolution training program tailored specifically for caregivers for veterans with SCI.

Caregivers and veterans with SCI will be involved in the design and development of this training program.

Dose Escalation Study of Intravenous Baclofen in Healthy Adult Volunteers
Robert Kriel, MD
University of Minnesota
$75,000 (one year)

The purpose of this study is to reduce some of the problems which sometimes happen in people who are taking baclofen.

Baclofen is the most effective and commonly used medicine to reduce spasticity or abnormal tightness of muscles that commonly occurs in people with spinal-cord injuries, traumatic brain injuries and cerebral palsy.

The body develops a reliance on baclofen and if it’s stopped suddenly for any reason, a potentially severe withdrawal syndrome can develop. Currently, baclofen can only be given by mouth or by an infusion pump into the spinal canal.

The goal of this study is to test an intravenous formulation of baclofen. The results of our study will be helpful for planning studies to design intravenous baclofen therapy to prevent baclofen withdrawal in people who may need to temporarily stop taking the medicine, and to manage people who are having baclofen withdrawal symptoms.

Targeting the Ipsilateral M1 to Improve Hand Opening-Closing after SCI
Toshiki Tazoe, PhD
University of Pittsburgh
$149,471 (two years)

The ability to open and close the hand is largely impaired in individuals with a cervical spinal-cord injury (SCI).

These movements are fundamental motor skills in daily-life activities such as eating, writing and many other object manipulations. Hand movements are mainly controlled by the motor cortex contralateral to the moving hand, but some involvement of the ipsilateral motor cortex has been demonstrated.

The goals of this proposal are to investigate the physiological contribution of the ipsilateral motor cortex to hand opening-closing movements in individuals with chronic incomplete cervical SCI and study strategies to elicit neural plasticity in the ipsilateral motor cortex to promote the recovery of hand function.

To achieve these research goals, we’ll conduct neurophysiological experiments using transcranial magnetic stimulation and peripheral nerve electrical stimulation techniques on individuals with and without SCI.

The proposed experiments will provide new knowledge on the neural substrates contributing to hand motor function and might contribute to develop novel interventional approaches to enhance the recovery of hand motor function after SCI.

Design & Development

Characterization of Intraparenchymal Pressures after SCI
Brian Kwon, MD, PhD, CSC
University of British Columbia
$150,000 (two years)

This research proposal is focused on the severe swelling of the human spinal cord that is typically observed after traumatic injury, which is poorly understood.

Characterizing the physiologic and biologic effects of this phenomenon and determining how they can be mitigated to reduce secondary injury will guide the optimal clinical management for these acute spinal-cord injury (SCI) patients.

To interrogate this phenomenon, we’ll utilize our recently developed large animal (porcine) model of SCI, which shares similar size and anatomic characteristics to the human spinal cord. This allows us to model the swelling and filling of the intrathecal space that is observed after human injury.

Fellowship

Therapeutic Strategies to Promote Musculoskeletal Recover After SCI
Fan Ye, PhD
University of Florida
$100,000 (two years)

Spinal-cord injuries (SCI) occur mainly among males, with a high prevalence in young adults.

SCI was once deemed irreversible and untreatable, but recent approaches have shown great promise in facilitating functional recovery. One promising strategy is to provide specific hormonal factors that improve muscle and bone recovery following SCI either alone or in combination with locomotor training in order to improve functional recovery.

Our proposed studies combine the high-dose testosterone (a male hormone) treatment with body weight supported treadmill or motor driven bicycle locomotor training to promote muscle, bone and neural recovery following severe chronic spinal-cord contusion in adult male rats.

In addition, we’ll co-administer MK-434 (a drug that limits the conversion of testosterone to dihydrotestosterone) with testosterone in order to prevent prostate enlargement, a primary side effect associated with testosterone treatment.

Restoring Somatosensory Function through Intracortical Microstimulation
Joseph O’Doherty, PhD
University of California-San Francisco
$98,771 (two years)

Individuals with spinal-cord injury (SCI) typically lose the ability to move their limbs, but they often lose limb sensations as well.

One key component of this lost sensation is proprioception, the feeling of where the body is in space. Even if there were therapies that could restore movement after SCI, without proprioception those movements would be slow and uncoordinated. The goal of this work is to develop strategies for restoring proprioception.

We focus on restoring proprioception in the context of brain machine interfaces (BMI), devices that harness brain activity to control assistive devices. We’ll develop and test “bidirectional” BMIs, which additionally create patterns of activity in the brain that are interpreted as proprioception.

Since these precise neural patterns aren’t known in advance, we’ll focus on the brain’s ability to learn to interpret new signals. If successful, this project will move us closer to restoring movement and sensation for persons with paralysis.

Fritz Krauth Memorial Fellow

Synchronization of Corticospinal Volleys after Tetraplegia
John Cirillo, PhD
University of Pittsburgh
$98,860 (two years)

The control of hand movements is largely disrupted in individuals with cervical spinal-cord injury (SCI).

During voluntary movement, multiple descending volleys are generated in the corticospinal tract, which travel from the motor cortex down to the spinal cord. An efficient synchronization of these descending corticospinal volleys is fundamental for proper generation of movement. Partial loss and demyelination of corticospinal axons after SCI is likely to impair synchronization of descending volleys.

At present, it’s possible to investigate noninvasively synchronization of descending volleys in humans by using paired-pulse transcranial magnetic stimulation (TMS) protocols. Using these protocols, we’ll first examine time-dependent intervals of descending volleys targeting finger muscles at rest and during voluntary activity after SCI. Second, we propose to promote hand motor function recovery after SCI by enhancing the synchronization of descending volleys.

The proposed research will increase our understanding on the mechanisms contributing to the generation of voluntary movement and may support the development of novel and more effective therapeutic interventions in individuals with SCI.

For more information on PVA Research Grants, visit pva.org.

 

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