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Research Developments

Reprinted from PN April 2011

What's the status of a cure for spinal-cord injury/disease? When will we see results?

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The PVA Research Foundation has announced FY 2011 grant awardees. The Foundation is devoted to putting grant money toward work that will advance the science needed to understand and treat spinal-cord injury and disease (SCI/D). Of the 65 applications the PVA Research Foundation Board of Directors received, 12 new grants were awarded, totaling almost $1.5 million.

Grants were awarded in four different research categories: basic science, design and development, clinical, and fellowships.

Basic Science

“Prevention of Recurrent UTI in Spinal Cord Injury”

Patrick Seed, MD, PhD

Duke University Medical Center, Durham, N.C.

$148,007 (2 years)

Many spinal-cord injuries result in the long-term loss of normal urinary bladder function, called neurogenic bladder. Routine catheterization of the neurogenic bladder is often needed to facilitate emptying urine from the bladder and prevent kidney damage. However, catheterization leads to bladder colonization with microbes and lifelong recurrent urinary-tract infections (UTIs). Chronic antibiotics fail to prevent recurrent UTIs and result in recurrences due to antibiotic-resistant bacteria.

This project’s goal is to develop new nonantibiotic approaches to prevent and treat UTIs in people with neurogenic bladders. We aim to understand the key reasons why neurogenic bladder leads to recurrent UTIs. We are also performing studies to understand if a natural antibacterial protein called lactoferrin is able to prevent and treat UTIs in the neurogenic bladder. Together, these studies may lead to fundamentally new approaches to help reduce chronic recurrent infections and improve quality of life for people with spinal-cord injury.

“Brain Machine Interface to Hand Grasp with Subdural and Epidural Signals”

Marc Slutzky, MD, PhD

Northwestern University, Chicago

$149,998 (2 years)

This project’s ultimate goal is to restore hand function to people with paralysis. Brain machine interfaces (BMIs), which decode electrical signals recorded from the brain, offer one way to bypass the area causing paralysis and directly control paralyzed muscles via electrical stimulation. The brain signals used in BMIs have been recorded with various levels of invasiveness. In general, there is a tradeoff between invasiveness and signal quality. We will investigate using two less-invasive signal types, subdural and epidural (below and above, respectively, the dura mater, which covers the brain), in a BMI in people with epilepsy who require placement of electrodes for their treatment. Our preliminary work suggests epidural signals may have similar potential to subdural signals to restore function with less risk to patients. We will decode grasp type, finger position, and grip force directly from the brain signals and then have the subjects control a computer hand using these decoders in a BMI. If successful, this project would move us closer to restoring grasp to paralyzed patients.

“Improving Treatment of Chronic Spinal Pain: Focus on Gabapentinoids”

Peter A. Smith, PhD

University of Alberta, Edmonton, Canada

$149,824 (2 years)

Lyrica (pregabalin) and Neurontin (gabapentin) are used to treat pain associated with spinal-cord, nerve, and brain injury. Unfortunately, these “gabapentinoids” tend to produce drowsiness, dizziness, and confusion, thus limiting their effectiveness. We aim to remedy this situation. For Lyrica and Neurontin to exert a pain-killing effect, they must get to the inside of a nerve cell. Unfortunately, the process by which they enter nerve cells is inefficient.

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This project seeks to improve gabapentinoids’ entry into nerve cells using a substance called capsaicin. This opens minute pores in the skin of the neuron that will let the drugs in. Because capsaicin affects pain nerves, we will be able to deliver large quantities of gabapentinoids to pain nerves without overloading the neurons responsible for causing dizziness, drowsiness, and confusion. This may lead to new therapeutic initiatives for the 75% of people who have chronic pain.

Design and Development

“Adjusting Computer Mouse Settings Automatically to Accommodate User Needs”

Heidi Koester, PhD

Koester Performance Research, Ann Arbor, Mich.

$150,000 (2 years)

The goal of this work is to enhance the productivity and comfort of computer access for people whose impairments affect their ability to use a computer mouse. While Windows includes several built-in settings that can make it easier for people with mobility impairments to use a mouse, adjusting these settings manually is typically tedious and frequently ineffective.

In this project, we will develop and evaluate a software tool for the automatic configuration of mice and other pointing devices. The software will assess current user performance with a mouse, recommend the appropriate Windows settings, and activate those settings, with user approval.

This project helps ensure users have the effective computer access they need in order to pursue their educational and vocational goals. It will also afford better access to computers outside the home or office, such as those in libraries or other public locations, giving people the flexibility to access any computer, anytime, anywhere.

“Evaluating the Effectiveness of Health Mechanics: A Self-Management Program for Individuals with Spinal Cord Injury”

Michelle Meade, PhD

The Regents of the University of Michigan, Ann Arbor, Mich.

$149,974 (2 years)

For people with SCI, secondary conditions can limit independence, decrease functioning, prevent community integration, and lead to expensive treatments and re-hospitalizations. However, they can be prevented or minimized with appropriate management—including performance of health maintenance behaviors and compensatory strategies.

Health Mechanics is a self-management program created by Dr. Michelle Meade to teach people with SCI the skills that will help them keep their bodies healthy and to manage their lives given their physical impairments. The basic skills or tools taught in this program are attitude, self-monitoring, problem-solving, communication, organization, and stress management. This pilot study will test to determine if receiving the self-management intervention improves self-regulatory skills and quality of life and reduces the number of secondary conditions.

Clinical

“The Effect of Postural Supports on Lung Capacity and Airflow Exchange”

Jessica Pedersen, MBA

Rehabilitation Institute Research Corporation, Chicago

$149,869 (2 years)

This will be a clinician-focused project that compiles statistical evidence-based data demonstrating efficacy of the postural trunk and abdominal support systems provided to people with SCI ASIA T5. The spirometry measures include forced vital capacity, maximum force expiratory flow, average force expiratory flow, forced expiratory volume, and peak expiratory flow. The positions that will be tested include:

- Slumped posture in wheelchair without added support

- Sitting upright in wheelchair without support (upholstery only)

- Sitting upright in wheelchair with posterior sacral lumbar support

- Sitting upright wearing an abdominal binder in wheelchair without support (upholstery only)

- Sitting upright wearing an abdominal binder in a wheelchair with posterior lumbar sacral support

Postural measurements for the five positions will be done using a goniometer and scoliometer. A survey will assess whether participants would use the supports in their daily lives.

“A Rehabilitation Program for Manual-wheelchair Users with Shoulder Pain”

Kristin Zhao, MA

Mayo Clinic, Rochester, Minn.

$150,000 (2 years)

People with SCI must use the upper body for all daily activities, including propelling their wheelchairs and transferring. Unlike the hip joint, the shoulder joint is not designed for repetitive activities or weight-bearing tasks. For this reason, it is reported that as many as 50% of people with SCI suffer from shoulder pain. We believe shoulder pain in this group is caused by undesirable shoulder-motion patterns due to muscle weakness and strength imbalances in the shoulder muscles.

This study’s goal is to eliminate shoulder pain and restore shoulder function in people with SCI through a comprehensive strengthening program. We will prescribe a 12-week exercise program that is accessible, with inexpensive equipment that can be used in the home. Exercises will be introduced to our subjects using biofeedback of muscle activity and joint movement. Subjects will receive further instruction on their exercise performance using videoconferencing via the Internet.

Fellowships

“Role of Exercise-Induced GDNF and Artemin in SCI-Induced Neuropathic Pain”

Megan Ryan Detloff, PhD

Drexel University, Philadelphia

$100,000 (2 years)

Neuropathic pain is a chronic, devastating, and complex condition that impairs the daily lives of more than two thirds of people living with SCI. After injury, the nerve fibers in the spinal cord are damaged and dysfunctional, causing incorrect signals to be transmitted to pain centers in the brain.

Research has shown that restoring the levels of neurotrophic factors—molecules that promote survival of sensory nerves—to normal levels in the spinal cord can reduce aberrant changes to sensory nerves and, most importantly, ease the feeling of pain.

The proposed research will improve understanding of how neurotrophic factors contribute to recovery of normal sensation. We will use exercise to stimulate neurotrophic-factor production in sensory nerves and the spinal cord and correlate the levels of these factors to the alleviation of pain.

In 2002, a highly distinguished award was named for Fritz Krauth, a 40-year Paralyzed Veterans of America member who made a significant donation to the PVA Research Foundation. During this grant cycle, Dr. Detloff received the 2011 Fritz Krauth Memorial Fellow for her work on this project.

“Regulation of Experimental Autoimmune Encephalomyelitis by FcgammaRIIB”

Fubin Li, PhD

Rockefeller University, New York, N.Y.

$99,688 (2 years)

Multiple sclerosis (MS) is a devastating and often disabling disease involving activated self-attacking immune cells and their damage to brain and spinal cord. FcgammaRIIB, a molecule present in many immune cells, functions like a brake to limit their activation. Loss of FcgammaRIIB leads to exacerbated experimental autoimmune encephalomyelitis (EAE), the mouse model of MS, implicating FcgammaRIIB-loss in the pathogenesis of EAE.

While many types of immune cells express FcgammaRIIB, little is known about how FcgammaRIIB-loss on specific cell types affects the progression and severity of EAE. This study will address this question using a series of novel mouse lines with engineered cell type-specific deletion of FcgammaRIIB. Another goal is to test whether EAE can be alleviated by increasing FcgammaRIIB levels. This study is expected to improve our knowledge about the pathogenesis of MS and the potential of FcgammaRIIB-based therapy.

“Manual Wheelchair Activities Associated with Shoulder Pain and Injury”

Melissa Morrow, PhD

Mayo Clinic, Rochester, Minn.

$100,000 (2 years)

Shoulder pain is very common in people with SCI who use manual wheelchairs. Most research that has investigated root causes of this shoulder pain occurred in a laboratory setting. To truly prevent shoulder pain, we need to leave the laboratory to identify the real risk factors that occur in daily life. The goal of this study is to identify those factors that lead to shoulder pain in manual-wheelchair users. To accomplish this goal, we will study the activities of daily living, forces on the hand, and body posture of manual-wheelchair users during one full day in their own environment. Data will be collected with special sensors and will not require participants to alter their normal daily routine.

Additionally, we will gather evidence on whether participants have current shoulder pain and/or injury. Information from this study will be used to guide prevention strategies and rehabilitation. 

“The Role of Gamma Delta T Cell Subsets in EAE and Multiple Sclerosis”

Sarah Polakow, PhD

Drexel University College of Medicine, Philadelphia

$100,000 (2 years)

The immune system has the daunting task of recognizing self from non-self, which requires identification of a plethora of foreign pathogens while maintaining tolerance to self-tissues. When this distinction goes awry, autoimmunity—reaction to self-tissue—occurs.

In people with multiple sclerosis (MS), myelin—the protective covering that insulates neurons in the central nervous system (CNS)—is targeted and destroyed by the immune system’s inflammatory cells. When motor neurons are demyelinated, paralysis occurs.

This project focuses on gamma-delta T cells, a highly specialized group of inflammatory cells in the cerebral spinal fluid and near lesions in MS patients. Using a mouse model of MS, we examine how these cells contribute to autoreactive inflammation in the CNS. We have identified two subsets of gamma-delta T cells in the CNS that, when activated, appear to have distinct and opposing roles. The working hypothesis is that if one subset is protective and the other is pathogenic, treatments directed toward balancing gamma-delta T cell subset functions could minimize pathological effects and possibly promote remyelination.

“Activation of Endogenous Neural Precursor Cells for SCI Repair”

Clara Penas, PhD

Miller School of Medicine of the University of Miami, Miami, Fla.

$50,000 (1 year)

SCI initiates a complex cascade of mechanisms leading to an acute loss of spinal-cord tissue across the lesion site. Consequent is the failure of neurological function. CNS has a limited capacity to generate new neurons and appears incapable of endogenously replacing those that are lost following SCI. In addition, the lesioned axons are unable to surmount the inhibitory environment of the lesion site to regenerate to their caudal targets.

This project will use a combinatory therapeutic approach involving clinically-used drugs and bioengineered scaffolds that will aim to enhance the survival, proliferation, neural differentiation, and migration of neural precursor cells to repopulate the lesion site. This treatment will also give a supportive bridge for host axonal growth.

Therefore, the approach will permit the replenishment and tissue regeneration after SCI, providing restoration of the neuronal circuitry and enhancing functional outcome.

Other Research Endeavors

From transplanting cells to regenerating damaged nerve fibers to designing adaptive canoe seats, the PVA Research Foundation supports innovative research and fellowships that improve the lives of people with SCI/D. A 501(c)(3) nonprofit, it funds five research categories:

- Laboratory research in the basic sciences to find a cure for SCI/D

- Clinical and functional studies of the medical, psychosocial, and economic effects of SCI/D, and interventions to alleviate these effects

- Design and development of assistive technology for people with SCI/D, which includes improving the identification, selection, and use

of these devices

- Fellowships for postdoctoral scientists, clinicians, and engineers to encourage training and specialization in the field of spinal-cord research

 

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