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Thread: Mayo Clinic Changes Treatment for Spinal Cord Injury

  1. #1

    Mayo Clinic Changes Treatment for Spinal Cord Injury

    December 29, 2011




    Supporting Neuronal Growth: Regenerative Neuroscience at Mayo Clinic
    Mayo Clinic scientists are providing nerves with a platform for neural regeneration, using advanced biomedical technology and novel methods of tissue engineering to manipulate neural growth factors, guidance cues, and the extracellular environment. Three integrated research initiatives are addressing regeneration in the spinal cord, the brain, and the limbs. Two of these projects—one fostering axonal extension across large-gap peripheral nerve injuries and one preventing cell death and promoting neural regeneration in the brain—are about to enter clinical trials. Work on spinal cord regeneration is being tested in animals.
    Making a Hostile Environment Permissive
    In the developing nervous system, nerve growth cones—the cone-like tips of axons and dendrites—extend and retract, "sniffing out" the molecules needed to help the cones reach and connect with their targets. A complex array of molecular guidance cues tell them whether to continue, to keep on their path, or to turn left or right. The extracellular environment and intrinsic cell signaling are primed to help them in their search and act as a compass on their journey.
    Neural growth factors and low levels of neural guidance cues are also available in the fully developed nervous system. However, an array of inhibitory factors create an environment that is hostile to regeneration in the CNS. In the PNS, it is the lack of a permissive pathway that prevents projection of axons across large gaps. Many of these inhibitory factors have been identified, and by eliminating them in the laboratory, researchers have been able to generate nerve cell growth in vitro. Translating this success into the human nervous system has been a major challenge.
    Enhancing Neural Growth
    Early, but unsuccessful, efforts at human nervous system regeneration in the 1990s focused on creating antibodies to counteract inhibitory factors. Mayo Clinic took a different approach. Led by Anthony J. Windebank, MD, a neurologist and molecular neuroscientist, Mayo researchers pioneered ways of reengineering autologous mesenchymal stem cells to enhance their ability to produce trophic and growth factors. Dr Windebank’s theory was that after implantation, the stem cells could serve as delivery vehicles for neural growth factors, promoting nerve regeneration. What was needed was a permissive environment that could sustain growth and, equally important, enable axons to find and connect with appropriate targets.
    Providing a Physical Scaffold
    Michael J. Yaszemski, MD, PhD, a Mayo Clinic orthopedic surgeon and biomedical engineer, developed a physical structure that could house such an environment. Made of a copolymer called polycaprolactone fumarate, it joins two compatible polymers never before brought together. The resulting synthetic tubing (Figure 1) provides a biodegradable scaffold between severed axons, within which neural growth factors, signaling molecules, and guidance cues can sustain new growth and axonal projection. It also provides physical channels through which axons can extend more readily (Figure 2, see page 4), helping to prevent undirected peripheral nerves from forming neuromas. The scaffold degrades naturally when axons reconnect, a process that can take weeks to months.
    Redirecting Guidance Cues
    Providing a permissive environment within the scaffold depends on overcoming inhibitory factors and directional miscues. For example, after nerve injury, soluble fragments of myelin components, such as myelin-associated glycoprotein, are released that prevent neurons from growing and can cause nerve growth cones to collapse. In addition to such growth-preventing proteins, other factors at the injury site may steer growing nerve tips in the wrong direction. Thus, even if growth is initially supported, neurons must be redirected toward their targets or they will not survive.
    John R. Henley, PhD, a Mayo Clinic molecular neuroscientist and director of the Neurodevelopment and Regeneration Laboratory, has devoted his career to identifying and manipulating the second messengers that regulate neurite growth and that transduce extracellular guidance signals through a cascade of intracellular events to mediate directional guidance. These are the cues that facilitate axonal attraction or repulsion and directional turning. Dr Henley and his colleagues have had success in altering certain second messengers to prevent misdirected axonal tip turning. For example, in an assay that elevates the intracellular second messenger cyclic adenosine monophosphate (cAMP), repulsive turning responses can be converted into attractive ones. He says that this work is directed at priming nerves to grow on inhibitory substrates by altering not only the external molecular environment, but also the intrinsic state of a neuron—something previously not thought possible.
    Clinical Initiatives
    Peripheral Nerve Regeneration
    Dr Yaszemski, a brigadier general in the US Air Force Reserves who has served as deputy commander of the hospital at Balad Air Base north of Bagdad, has had direct experience with the extensive limb wounds of soldiers in Iraq and Afghanistan. He and Dr Windebank serve as codirectors for nerve injury research in the Armed Forces Institute of Regenerative Medicine, a Department of Defense–funded consortium of 16 institutions to generate new treatments for war-wounded persons. Work at Mayo Clinic focuses on nerve regeneration. Within one year, in conjunction with Robert J. Spinner, MD, a Mayo Clinic peripheral nerve surgeon, Drs Windebank and Yaszemski will begin the first human clinical trials of the polymer scaffold implants at Mayo Clinic in Rochester, Minnesota.
    Spinal Cord Nerve Regeneration
    The spinal cord presents a particular set of challenges. As Dr Henley notes, neurons in the CNS face an environment that is more hostile to regeneration than do peripheral nerves. In addition, axonal growth must be bidirectional (both toward the brain and away from it), and scar tissue at the interface of the spinal cord and scaffolding exerts an extra-inhibitory environment. Drs Windebank and Yaszemski and their colleagues have applied the scaffolding technology to the injured spinal cord in animals. Dr Henley’s work in elevating the influence of second messengers to reprogram growth cones will help push growing nerves beyond the scaffolding and into the native spinal cord. He envisions a timed release of modulating factors and a second messenger cascade of calcium, cAMP, and other second messengers, to coordinate with the dissolving scaffolding tube as nerve tips reach the native spinal cord.

    http://www.mayoclinic.org/mcitems/mc...c5520-1010.pdf

    (This is investigative research being worked on. It is not a current registered human clinical trial.)
    Last edited by GRAMMY; 01-04-2012 at 03:22 AM.

  2. #2
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    Another good news but still away from trials for chronics i guess

  3. #3
    Quote Originally Posted by Jawaid View Post
    Another good news but still away from trials for chronics i guess
    What?? This clearly states they will begin a nerve regeneration trial within one year starting on the brain. Wouldn't large gap nerve regeneration be needed for chronic sci or is there a need for something else? Work on spinal cord regeneration is being tested in animals right now. I think this is very fantastic news and I appreciate their efforts on this (nothing to be sour about) We're getting some very good sci research help here!
    Last edited by GRAMMY; 01-03-2012 at 12:53 PM.

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    Really Grammy? Sorry i could not understand it dear.

    Hope this can be fruitful for us this year.

  5. #5
    Thanks Grammy - Very, very interesting.
    "It's not the despair, I can handle the despair! It's the hope!" - John Cleese

    Don't ask what clinical trials can do for you, ask what you can do for clinical trials. (Ox)
    Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature.

  6. #6
    another step in the right direction, excellent!!!

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    Again clinical trials for spinal injury away 5 to 10 years.

  8. #8
    Quote Originally Posted by Jawaid View Post
    Again clinical trials for spinal injury away 5 to 10 years.
    It's probably little to no consolation, but the newsletter from which the 5 - 10 year time frame comes from was published in 2010.

  9. #9
    Now, I wonder if Drs Yaszemski and Windebank could execute a clinical trial within DoD grounds where the FDA has no jurisdiction

  10. #10
    Quote Originally Posted by Fly_Pelican_Fly View Post
    Now, I wonder if Drs Yaszemski and Windebank could execute a clinical trial within DoD grounds where the FDA has no jurisdiction
    I'm hoping with the DOD involvement it will help them! I remember about a year ago, maybe longer, reading that Mayo announced formulation of a spinal cord injury team. If I'm not mistaken there were about 10 researchers names on the list and quite impressive.

    ***Perhaps I should put a disclaimer at the bottom of any science and research posts that they are not currently in clinical trials. (Some of it is investigative research not being put into humans yet). Not ALL research work being done in the neuro field should even go into human trials! But, it's interesting to learn about the work that is being done throughout the field. This particular post wasn't even about a clinical trial, so the information was mostly ignored... I sincerely think people get way too carried away with the clinical trial stuff instead of actually looking at the science and research itself. Taking that shortcut and ignoring it could be disasterous if we don't know the science and research and only focus on when the next person is to be injected with something just as quickly as possible with yet no idea of what it actually is. UGH!!!! That wouldn't be too short of the medical tourism going on overseas. Sometimes people have no idea of what they want to be injected with or thoughts about efficacy...(they mistakenly think any injection will do...) From some of the responses that are posted at times, I worry about the knowledge base and enlightenment on cure issues and research. It's of grave concern to me!

    If a clinical trial is actually starting for SCI, I put that in the chart for everyone to look over along with the data to study and links to at least start the information search. Not all clinical trials running are equally good. Good sound decisions can be made with a solid knowledge base. Without that you're in a crap shoot.

    I found the video valuable from a few days ago when the Mayo Clinic announced that steriods are no longer automatically in the treatment of trauma protocol for their patients or when other doctors call the center for advice on their trauma cases. It's important for everyone to keep up with the latest developments so we know what to do and expect. When the Flight for Life helicopter lands, it'd be pretty nice for people to have some knowledge base about SCI when the doctors call Mayo for help on the trauma cases that are presented there.
    Last edited by GRAMMY; 01-04-2012 at 03:25 AM.

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