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Granting Goals

Reprinted from PN/Paraplegia News April 2013

The PVA Research Foundation awards grants to continue searching for SCI/D treatments.

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The search to better understand, treat and even possibly find a cure for spinal-cord injury and disease (SCI/D) is a never-ending battle. Even though the fight may be long and hard, there is no shortage of people willing to take up that challenge, and Paralyzed Veterans of America (PVA) continues its efforts to help them.

The PVA Research Foundation is devoted to putting grant money toward work that will advance the various efforts to accomplish these goals. This year, the foundation awarded $819,771 in grants to seven new projects in four different categories, including basic science, design and development, clinical, and fellowships. More than 75 applications were received in search of these grants.

A highly distinguished award was named for Fritz Krauth in 2002. A 40-year PVA member, Krauth made a significant donation to the Research Foundation. The 2013 Fritz Krauth Memorial Fellow went to Denise Puga, PhD, a post-doctoral fellow in the neuroscience/SCI department at The Ohio State University.

Puga’s project, Stress and Glucocorticoids Exacerbate Recovery after SCI, focuses on improving data that will facilitate the design of new therapeutic interventions regarding how repeat stress affects the central nervous system structure.

Brief descriptions of this year’s grants follow.

Basic Science

Maladaptive Dendritic Spines, Neuropathic Pain & Spasticity after SCI/D

Andrew Tan, PhD 

Yale University

$149,213 (Two Years)

An unmet clinical need in veterans with SCI/D is the development of neuropathic pain and spasticity. The lab has focused on the theory that the damaged spinal cord wrongly “hardwires” the circuitry involved in neurological function.

Dendritic spines (microscopic receivers on nerve cells) change shape, size, and number after SCI. These structures can abnormally convert electrical information, leading to pain and spasticity.


The project of Alicia Hawthorne, PhD, concerns promoting regeneration after spinal-cord injury/disease.

The study has begun to investigate the effects of dendritic spine changes in the sensory and motor systems after SCI/D, which could help identify ways to therapeutically target pain and spasticity.

Successful completion of experiments will provide new perspectives in the study of SCI/D. It’s hoped this will accelerate the development of more effective clinical strategies for managing neuropathic pain and spastic conditions in the veteran and civilian population with SCI/D.

Design & Development

Development of Mobile Manual Standing Wheelchair

Gary Goldish, MD

Minneapolis VA Medical Center

$146,270 (Two Years)

Current manual standing wheelchairs don’t allow movement in the standing position. The purpose of this project is to develop a manual standing wheelchair that can be moved using the push rims in either seated or standing positions. The new wheelchair design will also have multiple gears, making it easier to move up slopes.

Six veterans with spinal-cord injuries will be involved in this project in a user advisory group. Early input from the group will help guide development of the wheelchair. The group will also evaluate the full-scale prototype at the end of the project.

Clinical

Two-Way Crossover Study of Oral & Intrathecal Baclofen in Healthy Adults

Robert Kriel, MD

Regents of the University of Minnesota

$75,000 (One Year)

The purpose of this study is to reduce some of the problems that sometimes happen to people 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 is to test an intravenous baclofen therapy to prevent withdrawal in people who may need to temporarily stop taking the medicine, and to manage individuals who are having baclofen-withdrawal symptoms.

A More Accurate Method to Estimate Renal Function in Spinal Cord Injury

Jennifer Lee, Pharm D

Southern California Institute for Research & Education

$149,298 (Two Years)

The National Kidney Disease Education Program recommends using the Cockcroft–Gault creatinine clearance or modification of diet in renal disease equation when determining dosages of drugs that are primarily eliminated by the kidneys.

However, neither equation considers the key factor of SCI/D: significantly reduced serum creatinine. Consequently, using such equations in people with SCI/D would result in gross overestimation of their renal function that will increase the risk of toxicity and/or adverse drug reactions.

Thus, the investigators have developed a new SCI/D equation that may better estimate renal function in SCI/D. However, the study was not devoid of limitations. The retrospective study had limited control of confounding variables, a small study population, and several assumptions. Thus, a prospective study in a larger population is needed to confirm and validate the previous findings in order to standardize the proposed SCI/D study equation in
clinical practice.

Fellowships

Promoting Regeneration After SCI/D Through Local Protein Synthesis

Alicia Hawthorne, PhD

Emory University

$100,000 (Two Years)

Nerve cells fail to regrow after spinal-cord injury. The goal of this research is to investigate a novel gene therapy strategy for spinal-cord injury to promote regrowth of nerve cells.

Models include a cell culture system and a mouse model of spinal-cord injury. We’ll test if increasing the proteins important for growth inside the nerve cell can provide robust re-growth after injury. This strategy focuses on transporting these proteins to the endings of the nerve cell, where the proteins are needed in order for the cell to grow.

This increase in proteins may drive the growth of the cell forward, which is critical for recovery, and in the future can be combined with other treatments to further optimize growth.

Stress and Glucocorticoids Exacerbate Recovery After SCI/D

Denise Puga, PhD

The Ohio State University

$100,000 (Two Years)

Relative to able-bodied individuals, people living with SCI/D experience increased bouts of major depression and anxiety, often resulting in suicide.

Even if SCI/D individuals don’t become clinically depressed or suffer from anxiety disorders, the unique challenges this population faces due to loss of neurological function (e.g., bladder/bowel control, sexual dysfunction) or neuropathic pain elicit prolonged recurring bouts of stress. How repeat stress affects central nervous system structure and neurological function after SCI/D is unknown.

Because the pathological consequences of stress vary between individuals and depend on environmental and genetic variables, two rat strains with genetically encoded differences in stress responsivity (i.e., Fischer and Lewis) will be used to determine the effects of stress and glucocorticoid release on anatomical, molecular, and functional (e.g., locomotion, pain) indices of recovery after SCI/D.

It’s expected that novel data will be generated that will facilitate the design of new therapeutic interventions.

Implementing Local Cooling to Reduce Pressure Ulcer Risk in People with SCI/D

Yi-Ting Tzen, PhD

University of Pittsburgh

$99,990 (Two Years)

Pressure ulcers are a prevalent secondary complication in people with SCI/D. They are caused by ischemia (lack or blood flow), and several factors increase pressure- ulcer risk. Increased skin temperature is one of the least explored risk factors.

This study’s purpose is to examine local cooling’s effectiveness at reducing the damaging effects of ischemia at the sit bones for people with SCI/D during seating. One side of the buttocks will be cooled to 77 degrees during seating, while the other will not have any temperature control (the temperature is expected to reach three to seven degrees higher than the cold side).

The skin blood flow will be measured at the sit bones to compare the severity of tissue ischemia between the two sides. Results from this study can be implemented into improved cushion/mattress design and clinical practice to prevent pressure ulcers in people with SCI/D.

Note: For information about the PVA Research Foundation, visit pva.org or contact Maureen Simonson, RN, MSN, director of PVA Research & Education, at maureens@pva.org. 

 

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