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  • The gift of motion

    BY JULiE METTENBURG | PHOTOGRAPHY BY MARK MCDONALD

    Two research projects at the KU Medical Center may provide new hope for the treatment of spinal cord injuries: not only to retain movement in patients’ arms and legs, but also to enable them to use their hands, stand or even walk again.

    An anonymous donor has provided $4 million to support the Spinal Cord Injury Repair Program in developing two novel approaches in restoring nerve communication using microelectronics and cellular regeneration.

    “To be able to stand up would be a major change in quality of life for many patients,” said Randolph J. Nudo, Ph.D., director of the Landon Center on Aging and one of the program’s lead researchers. “We want to go beyond that, but one step at a time.”

    The donor, a quadriplegic following a spinal cord injury several years ago, approached KU with a desire to fund neuroscience research that might lead to restored function after chronic spinal cord injury. Smith and colleagues identified five potential projects based on expertise in KU’s Institute for Neurological Discoveries (IND) and relevance to the donor. They narrowed the list to the two that provided the best chances for improvement.

    One gift, many benefits
    This research is inspired and
    supported by an individual
    donor, but it holds potential
    promise for thousands of others.
    spinal cord injury is costly,
    devastating and, currently,
    essentially untreatable.
    about 265,000 people in the
    united states are living with
    its effects, with about 12,000
    new patients each year. it
    affects primarily males who
    average 40 years old. They face
    reduced life expectancy and
    immense continuing medical
    costs. only a third of patients
    ever successfully resume
    employment, with just 11 percent
    working one year after injury.
     
     
    Peter G. Smith, Ph.D., director of the IND and the Spinal Cord Injury Repair Program, said the project brings researchers from basic science disciplines such as physiology, anatomy and pharmacology together with clinicians in neurosurgery, neurology, rehabilitation medicine and more. “This is not just about KU,” Smith said. “We’ve brought in key collaborators at K-State, Case Western Reserve University, Harvard University and the University of Washington. This is about building the best possible research teams to solve a very complicated problem.”

    The brain-spinal cord interface approach, led by Nudo, uses microelectronics to provide an artificial communication link from the brain to the spinal cord, a pathway that is severed in spinal cord injury. The regeneration strategy, led by Smith, is to discover a way to place new cells in the spinal cord that can replace damaged pathways. “Together, these short- and long-term fixes provide the greatest hope for individuals with spinal cord injuries,” Smith said. The early phases of the work must be performed in animals in order to perfect techniques and develop rigorous measurements to determine if therapies are working. The challenge now, for Nudo’s team, is mapping brain and spinal cord areas to connect; for Smith’s team, it’s engineering the proper cells to replace injured spinal cord cells.

    ANSWERS ON THE HEAD OF A PIN

    The next time you curse your cell phone, think twice: The same technology might hold the key to preserving motion after spinal cord injuries.

    Nudo has previously focused on developing therapies for stroke using neural prosthetics to bypass damaged areas of the brain. This project brings that approach to spinal cord injury.

    When the neural pathways that connect brain to limbs are severed, several structures remain intact: the parts of the brain creating signals, the neurons below the injury in the spinal cord that relay signals, and the muscles that would receive the signals. Therefore, a patient could retain basic motor function if implanted electrodes could record the brain’s electrical signals and send them past the damaged area, where they could activate an external limb, stimulate a muscle directly or stimulate neurons in the spinal cord.

    “Our work is trying to put those two things together,” Nudo said, “so someone literally would think about moving a limb, using the same neurons as before, and trigger the movement.” Implantable devices must be very small. Ten years ago, Nudo said, the technologies he’s using would have required an entire rack of computers. With microelectronics advances, his team can borrow from resources like cell phone technology.

    “Basically, we’re functionally reconnecting the brain and spinal cord with electronic devices,” he said. “We are designing circuits like a computer on the head of a pin.”

    A BRIDGE OF CELLS

    Unlike nerves outside the central nervous system, the nerves in the spinal cord cannot regenerate or repair themselves. Smith’s team is working on a treatment involving new cells with the ability to repair the damage for good.

    “A more permanent treatment would be reconnecting those wires, which means replacing dead cells,” Smith said. “If we can discover the right kinds of cells and the right technique to move them back into the spinal cord, we can get them to create new pathways and restore function below the lesion.”

    Smith’s team takes adult skin or blood cells and genetically reprograms them into stem cells, which can then become any other kind of cell. The IND partners with KU’s High Throughput Screening Laboratory in discovering drugs that can coax these stem cells to become the right type of neurons for repairing spinal injury; testing in animals will ensure they perform appropriately. The goal is to take a patient’s own easily obtainable cells, turn them into stem cells, and then encourage them to become cells that can be transplanted to repair a spinal cord injury.

    DONOR PARTNERSHIP DRIVES RESEARCH

    This project represents an unusual way to fund research. The donor had expressed interest in supporting research on two levels: He wanted to keep his support local rather than send it to research centers in other cities, and he wanted to partner with a top-notch scientific institution able to conduct cutting edge research related to spinal cord injury.

    KU’s Institute for Neurological Discoveries, a new model developed with just this kind of purpose in mind, was poised to work with him. To prepare for potential opportunities, the IND formed in 2008 after identifying research strengths at the medical center and affiliated regional institutions. Six specialties were identified addressing some 22 conditions, spinal cord injuries among them. With appropriate funding, Smith said, the IND could become preeminent in any of these areas of research.

    He said relatively few institutions have adopted this partnership model. “Donors have specific endpoints in mind, and we’ve developed specific milestones that we believe will take us toward those endpoints,” he said. “We’ve done this with the highest level of scientific integrity, so it’s really good science, but we also have catered to the needs of the patient.”

    Nudo said the scientific community at KU is grateful for the opportunity to develop this program, which could not have happened without this donor’s help. “It brought together scientists and clinicians who normally don’t work together to work single-mindedly on a project, and created the focus for all of us to think about a single goal,” he said. “It’s bringing a lot of visibility to the IND and to KU neuroscience in general.”

    Smith said, “Suddenly, you’re not working on a grant from the National Institutes of Health. You’re working for someone—a patient—and you understand the goals, hopes and desires, the urgency with which they would like to see some restoration of function.”

    He said the current NIH funding situation is unpromising. Many good projects are not funded, which doesn’t tend to open up much new exploratory science.

    However, donations like this one create opportunity for researchers to work on projects NIH might deem too risky. And success would likely help KU and the IND obtain future additional funding from NIH, the Department of Defense and others, bringing new opportunities.

    The IND was set up for just this purpose, Smith said, with teams preassembled and resources in place to respond rapidly. “This is the culmination of exactly what we were trying to accomplish,” he said. “It serves as a template for people as a way to get involved: You can make a difference.”

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    Peter Smith, Ph.D., holds a slide containing sections of the injured spinal cord of a rat.


    Peter Smith and Dora Agbas, Ph.D., examine sections of injured spinal cords. Agbas is a research assistant professor of molecular and integrative physiology.


    Smith’s team took a patient’s skin cells, converted them to stem cells, and induced them to grow into these adult nerve cells.


    Randolph Nudo works to map areas of the brain that send signals to muscles. He is assisted by Shawn Frost, Ph.D., research assistant professor of molecular and integrative physiology.


    “Basically, we're functionally reconnecting the brain and spinal cord with electronic devices.” — Randolph Nudo



    YOU CAN HELP

    To support this research or any other program at the KU Medical Center, contact Stephanie Grinage, 913-588-5552 or sgrinage@kuendowment.org, or visit kuendowment.org/kumc.
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