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Inspired Research

Reprinted from PN April 2016

Paralyzed Veterans of America continues its mission of changing lives and building futures by supporting a new year of innovative research

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The Paralyzed Veterans of America (PVA) Research Foundation maintains a strong and firm commitment to support groundbreaking research that improves the lives of everyone with spinal-cord injury and disease (SCI/D).

The foundation recently awarded seven grants, totaling almost $900,000, to scientists and researchers across the nation who are dedicated to leading the charge of discovering novel treatments and potential cures for SCI/D. 

Grants are offered in four categories, which are basic science, design and development of assistive devices, clinical applications, and postdoctoral fellowships to foster the development of career SCI/D investigators, which are crucial to advance this field.

Following are brief descriptions of the 2015 PVA Research Foundation grant awardees and their respective studies: 

Basic Science

Astrocyte Glutamate Transporters & Chronic Neuropathic Pain Following SCI

Angelo Lepore, PhD

Thomas Jefferson  University (Philadelphia)

$150,000 (two years)

Stem cell transplantation-based replacement of astrocytes is a novel and potentially powerful therapeutic strategy for central nervous system diseases such as spinal-cord injury (SCI).

In this PVA project, we’re testing such an approach for mitigating SCI-induced neuropathic pain. Development of neuropathic pain occurs in a significant portion of patients following SCI, resulting in debilitating and often long-term physical and psychological burdens. With the goal of developing a clinically translatable therapy for patients, we are testing transplantation of astrocytes derived from induced Pluripotent Stem (iPS) cells into a cervical contusion mouse model of SCI.

These iPS cells represent an exciting and clinically relevant technology for homogeneous derivation of mature cell types in large quantities for applications such as transplantation, importantly in an autologous fashion from the eventual patient recipient. It’s critical to test their therapeutic efficacy in affecting key functional outcomes critical to patients, such as neuropathic pain in SCI models.


Sarah Moyon, PhD

A Novel Combinatorial Therapy to Overcome Paralysis after SCI

Steve Perlmutter, PhD

University of Washington

$150,000 (two years)

Movement deficits constitute one of the most debilitating consequences of SCI, but current treatments produce limited improvement. 

This project will evaluate a novel combinatorial therapy to restore voluntary arm and hand movements after cervical SCI. The therapy modifies the connectivity and function of neural pathways above and below the injury by facilitating and directing natural mechanisms of learning. In a rat model of SCI, localized activity-dependent electrical stimulation and pharmacological agents will be delivered to the spinal cord to induce plasticity in specific, movement-related circuits.

The therapy is designed to produce lasting recovery; that is, improvements in movement abilities that persist after the treatment is ended.

Clinical Applications

Effect of Vibration Exercise on Upper Limb Strength, Function & Pain

Alicia Koontz, PhD

University of Pittsburgh         

$149,781 (two years)

Exercise with a whole-body vibrating platform has been found to increase lower-body muscle strength, power and performance among recreational to elite athletes. More recently, vibrating dumbbells have been developed to provide a more direct application of vibration to the upper limbs.

The purpose of this study is to evaluate the effectiveness of a novel vibration dumbbell exercise program over traditional dumbbell exercise in improving upper limb strength, function and pain.

Twenty-four wheelchair users with paraplegia will participate in a supervised 12-week strength training program consisting of dumbbell exercises designed to support propulsion and transfer activities. Twelve individuals will use the vibration dumbbell, while the other 12 individuals will use a standard dumbbell.

The study aims to show that vibration-based training provides for a more effective and efficient solution to building muscle work capacity for weight-bearing tasks and for protecting the joints from overuse and aging effects.

 

Functional Spasticity Management in Individuals with Spinal-Cord Injury

Dimitry Sayenko, PhD

UCLA David Geffen School of Medicine         

$75,000 (one year)

SCI results in a reorganization of spinal circuitry, which starts immediately, persists for months and often leads to spasticity and rigidity. Functionally, these alterations can negatively impact posture, disrupt daily activities and sleep patterns and significantly encumber caregiving. There’s currently no anti-spastic treatment available which would ameliorate the negative effects of spasticity and concurrently promote motor function in individuals with SCI. 

Using a combination of non-pharmacological neuromodulatory techniques, this proposal will investigate effects of transcutaneous electrical spinal-cord stimulation delivered during upright standing on the neurophysiology of the spinal cord in individuals with SCI who have some level of ambulation. A deeper understanding of these effects will provide new knowledge necessary to begin translation of the novel therapeutic strategy to clinical rehabilitation programs, where decreased co-contractions, dyssynergies and improved voluntary control can produce better functional outcomes.

 

Design & Development

Development & Testing of a Bed-Integrated Scale for Paralyzed Veterans

Jonathan Pearlman, PhD

University of Pittsburgh         

$146,959 (two years)

The obesity epidemic in the United States shows no signs of abating, and individuals with disabilities, specifically those with lower-extremity mobility disabilities such as wheelchair users, are 2.5 times more likely to be obese compared to the rest of the population.

Multiple studies have confirmed that frequent self-monitoring of weight improves the ability to lose and manage weight. Despite their increased risk of obesity, the benefits of weight self-monitoring have not been available to wheelchair users because of technical barriers to self-weighing.

To address this major technical barrier, the E-Scale, which is a bed-integrated body weight scale that passively and automatically collects and archives the body weight of the bed occupant, has been prototyped and bench-tested.

 

Postdoctoral Fellowships

Astrocyte Regulation of Intraspinal Plasticity & Motor Recovery After SCI

Joshua Burda, PhD

Regents of the University of California

$100,000 (two years)

In the United States, nearly 13,000 people each year experience a debilitating spinal-cord injury, which results in disability that prevents them from being able to perform essential daily functions, including walking, reaching, grasping and urination. Although many patients experience varying degrees of spontaneous recovery after injury, a lack of understanding of this remarkable process has prohibited the development of therapies for treating SCI patients with enduring neurological dysfunction.

The proposed research will provide critical insight into the biochemical and cellular mechanisms that regulate spontaneous recovery after SCI. This study will aid in the
discovery of new thera-
peutic targets for treating
neurological disability
that occurs after SCI, stroke or brain injury, as well as that brought on by neurodegenerative diseases that affect the brain and spinal cord such as multiple sclerosis.

 

2016 Fritz Krauth Memorial Fellow Award Recipient

DNA Methylome & Hydroxymethylome of Oligodendrocytes During Remyelination

Sarah Moyon, PhD

Icahn School of Medicine at Mount Sinai                  

$100,000 (two years)

Promoting myelin repair is the best-known means to prevent axon degeneration in spinal-cord injuries and diseases, including spinal-cord transection, multiple sclerosis (MS) and amyotrophic lateral sclerosis.

In the adult central nervous system, the main remyelinating cells are the oligodendrocyte progenitor cells (OPC). Their differentiation into mature myelinating oligodendrocytes (OL) is controlled by the dynamic expression of specific genes, named transcription factors (TF). A better understanding of how the TF are regulated from OPC to OL is essential to be able to target and enhance adult OPC repair capacities.

DNA methylation and DNA hydroxymethylation are major epigenetic regulators of gene expression, including TF expression. We will study the role of DNA methylation and hydroxymethylation in adult OPC, in physiological conditions and in mouse models of MS. This research will provide more information regarding adult OPC properties, which are capital to design future therapies capable to enhance remyelination and neuro-repair.

For more information on the PVA Research Foundation, visit pva.org.   

 

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