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Mayo Clinic Changes Treatment for Spinal Cord Injury

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    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; 4 Jan 2012, 3:22 AM.
    http://spinalcordresearchandadvocacy.wordpress.com/

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

    Comment


      #3
      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; 3 Jan 2012, 12:53 PM.
      http://spinalcordresearchandadvocacy.wordpress.com/

      Comment


        #4
        Really Grammy? Sorry i could not understand it dear.

        Hope this can be fruitful for us this year.

        Comment


          #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.

          Comment


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

            Comment


              #7
              Again clinical trials for spinal injury away 5 to 10 years.

              Comment


                #8
                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.
                stephen@bike-on.com

                Comment


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

                  Comment


                    #10
                    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; 4 Jan 2012, 3:25 AM.
                    http://spinalcordresearchandadvocacy.wordpress.com/

                    Comment


                      #11
                      The Future of Spinal Cord Research at Mayo Clinic

                      Mayo provides important base support for SCI research projects by funding necessities not funded by external grants such as space, infrastructure, microscopes, centrifuges, electrophysiological and other critical equipment.

                      Dr. Windebank has devoted most of his research career to understanding the mechanisms of peripheral nerve disease. He has extensive knowledge in how peripheral system Schwann cells stimulate regeneration after injury and was well aware that spinal cord nerve fibers also have the capacity to regenerate, but that many efforts have been thwarted by a cellular process that inhibits regeneration and promotes scarring.
                      Dr. Yaszemski is an expert in engineering a variety of polymers that are used as scaffolds to support new bone growth. He is also a firm believer in research that is initiated by patients who have a problem that needs to be solved. As a spine surgeon, he is frustrated that the best he can currently offer a person who comes in with an acute spinal injury, is stabilization of the bony spine that will allow the person to function with paralysis.
                      In casual discussions the two physicians wondered how they could synthesize their combined clinical skills with their cellular biology and engineering expertise and launch an effort to help patients with SCI. Just two years later, they began seeing promising results in studies that evolved from their collaboration.
                      "Thus far we've successfully implanted a scaffold in animals, shown that it supports and directs growth, and that it functions as a delivery system for drugs." Michael Yaszemski, M.D., Ph.D.

                      Orthopedic surgeon, Bradford Currier, M.D., and neurosurgeons Richard Marsh, M.D., and Robert Spinner, M.D., help plan experiments and keep the team focused on translating the science to humans.
                      To simulate spinal cord injury a small section of a spine is surgically excised from an anesthetized rat. It is replaced with a trellis-like, biodegradable, polymer scaffold designed to anchor nerve cells, deliver drugs that promote nerve regeneration, and dissolve after a predetermined time to make room for more nerve growth. "We're using polymer chemistry to find the ideal combination of plastics," says Dr. Yaszemski. "And we have designed and constructed a variety of these mini scaffolds. Now we're ready to test them to find the architecture that produces maximal nerve growth."
                      Another variable is sorting out which compounds do the best job of promoting nerve growth.
                      "We know that Schwann cells promote nerve growth so we harvest them from the peripheral nervous system and load them into the polymer scaffold," explains Dr. Windebank. "We also introduce neurotrophins - protein growth factors that promote nerve growth by blocking natural cell death. And we are experimenting with compounds that inhibit scar formation."
                      Three months after they injected Schwann cells into rat spinal cords, the research team observed as many as 5,000 nerve fibers growing throughout the length of the polymer scaffolds. There are hundreds of thousands of nerves in a normal spinal cord but Dr. Windebank estimates that it will be possible to restore function with ten percent of the normal number.
                      Collaboration with the Spinal Nerve Regeneration Project
                      Mayo researchers devote much of their time to educating future leaders in science and educational duties frequently lead to further scientific collaboration. For example, Drs. Windebank, Sieck and Yaszemski are all members of the thesis committee of a graduate student who is working on the polymer scaffolds an activity that keeps them abreast of each other's projects.
                      "Neuron target cell interactions have been best characterized in the motoneuron muscle area," says Dr. Sieck. "Potentially, motoneurons can pick any muscle fiber they want to innervate but they choose very specific types of muscle fibers that express the same contractile and metabolic proteins. The same problem exists for nerve axons in the spinal cord as they regrow following SCI. As we increase our understanding of the mechanisms by which neurotrophins mediate neuron-target cell interaction, we can apply that knowledge to developing therapies that will help Drs. Windebank and Yaszemski to steer a newly regenerated nerve in the right direction."
                      While encouraged by their progress, Dr. Windebank cautions that they must find a way to guide nerve terminals to make contact with the correct nerve ending before function can be restored.
                      "Thus far we've successfully implanted a scaffold in animals, shown that it supports and directs growth, and functions as a delivery system for drugs," says Dr. Yaszemski. "That says nothing about the nerve fibers actually functioning."
                      Slobodan Macura, Ph.D., a biochemist and an expert in nuclear magnetic resonance microscopy and spectroscopy, helps investigators judge their progress by producing images of the tiny polymer scaffold. Together with spectroscopy studies, he is able to provide information on the composition and concentration of metabolites in body fluids, cells, tissues, and organs. Other basic scientists at Mayo are conducting research that may help when the team is ready to begin the complex process of restoring function.

                      http://discoverysedge.mayo.edu/spina...jury/index.cfm


                      (This is investigative research being worked on. It is not a current registered human clinical trial.)



                      Last edited by GRAMMY; 4 Jan 2012, 3:17 AM.
                      http://spinalcordresearchandadvocacy.wordpress.com/

                      Comment


                        #12
                        Thanks Grammy!

                        Looks like we can see acceleration in SCI Cure Research field!

                        More & more teams , labs and doctors, more and more king's horses and king's men trying to put us, Humpty Dumpties, together again!

                        By 2015 we can see real, proven hope ...

                        Living in a dream
                        www.MiracleofWalk.com

                        Miracles are not contrary to nature, but only contrary
                        to what we know about nature
                        Saint Augustine

                        Comment


                          #13
                          I think we have lots of fine researchers that are working in the field. Their advancements will be critical for good outcomes for us. I like reading about their progress as they put the pieces back together.
                          http://spinalcordresearchandadvocacy.wordpress.com/

                          Comment


                            #14
                            I would like to know the clinical evidence Dr. Huddleston has to back up his opinion that Methylprednisolone is not effective.

                            I received it after a severe fall and am ASIA C.

                            Comment


                              #15
                              Originally posted by GRAMMY View Post
                              I think we have lots of fine researchers that are working in the field. Their advancements will be critical for good outcomes for us. I like reading about their progress as they put the pieces back together.
                              exactly... me too...
                              I like that expression - "they put the pieces back together" ...
                              In opposite dimension world we are connected than broken than connected than born than finish in big bang ...
                              www.MiracleofWalk.com

                              Miracles are not contrary to nature, but only contrary
                              to what we know about nature
                              Saint Augustine

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