Fast Track

UofL faculty members Scott Whittemore, Ph.D., Christopher Shields, M.D., and Susan Harkema, Ph.D., share a vision for improving the lives of spinal cord injury patients that has brought them together to form a dynamic leadership team for the Kentucky Spinal Cord Injury Research Center.

Whittemore, a neuroscientist, leads a basic research program targeted at finding ways to regenerate nerve tissue and repair damaged spinal cords. Shields, a neurosurgeon, works with a team developing new surgical techniques, treatments to be used immediately after an injury and other clinical applications of the center's research. Harkema, a rehabilitation specialist, studies the mechanisms that allow humans to walk and designs therapies aimed at restoring function in injured patients.

In a hallway outside the KSCIRC labs in UofL's Medical-Dental Research Building, a mission statement hangs on the wall: "We are dedicated to developing successful spinal cord repair strategies in the laboratory that can be taken to the clinic in a timely and responsible fashion."

It's not simply rhetoric. Whittemore, Shields and Harkema mention the mission in casual discussions about ongoing research, use it as context for decision-making and look to it as a guide to prioritize their work.

Late this summer, KSCIRC achieved three major milestones within just a few weeks. First, the National Institutes of Health announced a Centers of Biomedical Research Excellence (COBRE) Grant for $10.4 million over five years. This renewal extended an $8.5 million grant awarded to the center in 2000 and is the first major center grant to be renewed at UofL.

Second, Whittemore and colleagues in his laboratory published a study in the Journal of Neuroscience that demonstrates significant potential for a combination therapy that can repair the spinal cord by regenerating a protective coating on the nervous system.

Finally, Susan Harkema moved her laboratory from UCLA to Louisville, joining KSCIRC as the Owsley B. Frazier Chair in Neurological Rehabilitation, completing the center's leadership team and extending its reach into the field of rehabilitation.

These three milestones contributed to a critical mass - the aggregation of resources, personnel and a growing reputation - that UofL and the Louisville Medical Center are achieving in the field of spinal cord injury (SCI) research and treatment.

"We are seeing the extraordinarily positive capability develop of being able to treat all stages of injury here in the Louisville Medical Center," says Stephen Williams, CEO of Norton Healthcare, which provided much of the center's initial funding. "We are able to make something happen that we wouldn't be able to do alone.

Quality of Life

"This is a devastating condition," says Shields, who holds the Norton Hospital Chair in Neurosurgery at UofL. "There are about a quarter of a million people in the U.S. with some paralysis due to SCI - that's about 11,000 new injuries a year. These are young adults, for the most part, and their lives and those of their loved ones are changed forever. The lifetime 
costs of treatment are in the millions of dollars.

"If we can do anything to help these people live better, live more independently, live with dignity, that's something to be proud of."
Whittemore stresses that better quality of life is central to the work done at KSCIRC.

"The general public thinks that curing SCI means that patients will get up and walk, but when we talk to patients and their families, that's not the first goal that they mention. They want better bowel and bladder function, they worry about sexual function because many of them want to have families. They talk about more upper-body mobility, being able to do more activities of daily living without help, being able to work.

"These are the quality-of-life issues that we hope we can impact."

This doesn't mean that mobility or walking aren't important, says Cindy Norton, an SCI advocate with the organization Friends for Michael. But a measure of independence and dignity is uppermost in the minds of those
with SCI.

"They tell us, 'I don't care if I ever walk again, I just want to be able to pet my dog and do things for myself,' " she says.

Whittemore, Shields and Harkema are unanimous in their view that every discovery and every incremental improvement in function is important. The interactions between the various components of the nervous system are very complex, and seemingly small advances in different areas of inquiry may, in combination, add up to a significant improvement in function for SCI patients.

Return on Investment

These considerations drive KSCIRC's research agenda from the lab to the clinic.

"We have been very strong in basic science," says Whittemore, who notes that the state's Research Challenge Trust Fund has been instrumental in helping the center meet this need.

The fund, known informally as Bucks for Brains, matches state money with private donations to attract top faculty to UofL.

"This is a case where the Bucks for Brains program has really paid off in our ability to recruit and retain a team of top scientists and researchers," he continues. "We have deliberately tried to hire people whose work creates synergies with the research already in place. This a very collaborative enterprise."

Whittemore has held the Dr. Henry D. Garretson Chair in Spinal Cord and Head Injury Research since he joined UofL in 1998 from the Miami Project to Cure Paralysis. In addition to serving as scientific director, he directs the Molecular Neurobiology Laboratory, which focuses on reversing the molecular damage caused by SCI.

"Injury creates an ecosystem environment where molecular changes damage or destroy key components of the nervous system that carry signals to and from the brain," he says. "My lab focuses on ways to understand these mechanisms and develop strategies to replace neurons, axons, myelin and the vascular infrastructure that carries oxygen to these tissues."

His most recent research collaboration focuses on myelin, a coating that protects the nervous system much like the insulation around an electrical cord.

When myelin is damaged or destroyed by SCI, the nerves surrounding the spine cannot adequately conduct signals to and from the brain.

Whittemore found that stem cells can develop into cells that make myelin, which in turn grow and migrate to the damaged tissue. The new cells grow even faster when combined with a gene therapy that boosts production of two substances that help nerves survive and mature, he says.

"Other scientists have suggested this technique, but our study is the first to show that it really works," says Whittemore.

Basic science is, however, just the beginning of KSCIRC's vision.

"This isn't science for science's sake," says Whittemore, "Basic, clinical, and rehabilitation research are all intimately related. Observations with patients drive new experiments in the laboratory."

Shields agrees. His Spinal Cord Repair and Regeneration Laboratory conducts research on a broad spectrum of therapies and technologies for SCI repair. Recently, the lab has explored surgical and pharmaceutical therapies to prevent syringomyelia, a post-paralysis condition that can cause extensive damage to the neural tissue of the spinal cord. He and his colleagues are also working on a number of clinical applications, including use of magnetic resonance imaging to demonstrate the real-time flow of cerebrospinal fluid.

"We anticipate more therapies moving from basic science to clinical research as we continue to make progress," says Shields. "This is one reason why we are so pleased to have recruited Dr. Harkema, whose groundbreaking clinical rehabilitation research is a superb addition to the portfolio of expertise we are developing at KSCIRC."

Harkema's research focuses on neural plasticity and specifically addresses the spinal cord's capacity to "re-learn." By designing and applying rehabilitative therapies that re-teach patients to step and to walk, then measuring the effect of the activity on the nervous system's ability to change over time, she hopes to capitalize on the spinal cord's tremendous potential to play a role in improved function after injury.

"Many of the negative consequences of being in a wheelchair can also be avoided through these therapies," says Harkema. "We are finding that patients enjoy overall better health and quality of life. This kind of activity can keep them from developing, or lessen the severity of, common pulmonary, cardiovascular and metabolic problems."

By themselves, these scientific and clinical advances represent a significant return on investment in terms of quality of life and better health for SCI patients. Even in strictly financial terms, KSCIRC has achieved tremendous success. An initial investment of $9 million by UofL and the Commonwealth - both through Bucks for Brains and a state-sponsored fund called the Kentucky Spinal Cord and Head Injury Research Trust - has yielded more than $32 million in extramural funding by KSCIRC endowed chairs and other investigators.

State Sen. Tim Shaughnessey says this success is garnering attention nationally.

"We were recently invited to New Jersey to talk about the achievements of our spinal cord research programs and the funding model that we have with the Kentucky Spinal Cord and Head Injury Research Trust. It makes me proud that a program here in Kentucky is getting outstanding results and is considered one of the best in the nation."

Compassionate Roots

Shaughnessey's involvement with SCI research and public policy goes back more than 10 years.

"It started with compassion from an ordinary person," he says.

In January 1994, his niece was injured in an automobile accident while attending college in Mobile, Ala. After initial treatment in Mobile, she was brought to Louisville for additional surgeries at Jewish Hospital and then transferred to the Frazier Rehab Institute, where she was visited by a family friend, UofL neurosurgeon Christopher Shields.

"Dr. Shields wasn't her physician, but he came to see her and told the family about some research underway at the Miami Project to Cure Paralysis," says Shaughnessey.

Intrigued, he called Shields and learned that the Florida legislature funded this research program through a surcharge on speeding tickets. That was all Shaughnessey needed to hear. He took the idea to the General Assembly, which enacted legislation creating the Kentucky Spinal Cord and Head Injury Research Trust to allocate funds to the University of Louisville and the University of Kentucky with the goal of finding a cure for paralysis.

Another early partner was Norton Healthcare, which helped recruit Whittemore to UofL.

"This was before Bucks for Brains - there were no matching state funds at the time - but our board saw the vision and believed that we could help build a center in Louisville for advancing work on SCI," says Norton CEO Steve Williams.

"We felt very good about taking that leap of faith to expand the research agenda by providing support for recruiting Scott Whittemore from the Miami Project to the University of Louisville."

Norton has contributed more than $3.3 million to spinal cord research at UofL since, much of which has been matched through Bucks for Brains.

"Dr. Shields and Dr. Whittemore are both very careful to manage expectations," Williams says. "We know that developments in advanced clinical care and interventions for SCI patients will be evolutionary, not revolutionary. That said, it's one of the top research labs of this kind in the nation, and it is extraordinarily exciting to realize that a lab right here in Louisville could be the site for major advancements."

That realization motivated Owsley Brown Frazier and the Frazier Rehab Institute to partner with UofL in Harkema's recruitment, offering her the post of clinical research director at Frazier.

"Dr. Harkema is an outstanding addition to KSCIRC and to Frazier Rehab Institute," says Joanne Berryman, a senior vice president at the institute's parent organization, Jewish Hospital, and St. Mary's HealthCare. "It's a great example of what we can accomplish at the Louisville Medical Center through working together to build research and clinical expertise in an important area. We have critical mass to attract the very best in the field."

Looking ahead

One of the keys to staying on top is attracting outstanding graduate students and postdoctoral fellows to the Center.

"One of the really exciting things is that we have attracted several Kentucky natives back to the state," Whittemore says.

Jason Talbott, an Oldham County native, received his bachelor's degree from Stanford but is currently enrolled in the M.D./Ph.D. joint degree program at UofL and completed his doctoral research at KSCIRC.

"I considered going to Dartmouth or U.S.C., but my experience at UofL has been fantastic," Talbot says. "I have been working on the myelination research in Dr. Whittemore's lab, and I really believe that we are on the verge of making a significant difference for these patients. The opportunity to do research that has clinical relevance has helped me focus my career objectives."

Rebecca Smith, a postdoctoral fellow at KSCIRC, agrees. While completing her Ph.D. in neuroscience at Tulane, she saw the work being done by KSCIRC at a conference and was intrigued.

"I was interested in SCI because in grad school I worked on chronic pain models, and a lot of people with SCI have chronic pain," she says.

Smith, a Louisville native who earned her undergraduate degree at Centre College, is working in David Magnusson's lab on animal locomotion research that has potential for helping develop new rehabilitation therapies for SCI patients. She rates the experience highly.

"Dr. Magnusson is very hands-on and asks our opinions and advice. He sets a great example for scientific collaboration."

Strategic Growth

Each year, KSCIRC's researchers update a five-year strategic plan. Whittemore and Shields see this planning as a key factor in maintaining the center's momentum. They came away from this year's session with goals for strategic hiring in areas that will benefit multiple aspects of the program, for new research funding and for key infrastructure improvements.

"We achieved the goals of our first five-year plan in three years, exceeded our expectations in the second, and are moving forward on the third," says Whittemore.

"There's plenty to be excited about."