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Thread: Living Jumper Cables: Lab-Grown Nerves Promote Nerve Regeneration After Injury

  1. #11
    Quote Originally Posted by rjames View Post
    Dr, Young, thank you for the comprehensive reply to my question and the tip about the "Google Scholar" search I have just been using the standard google search method.

    You really hit the nail on the head about the translational research issue, I never really understood beyond the scarcity of funding why good solid research projects never seem to move beyond the lab. I hope this changes soon otherwise all the great research going on will never see the light of day. Thank you for your efforts with regards to trying to change this by taking clinicians to China to see what's possible.

    I actually contacted Dr. Martin a few weeks ago about his work and his future plans, he mentioned he was going to move it to larger animals but had no specific time line to do so. I started thinking about what some of the top nerve rerouting clinical specialists would think of this method so I did a search, came up with a list of names and contacted one of them in Europe, he felt that it probably would not lead to much success. I think he is the type you were referring to, not intrested in taking the time or the risk to look into it. Do you know of anyone in china that is doing anything like this? Dr. Zhang or Dr. Xiao?

    Thanks again for your time,

    John Martin is a basic scientist. He is NOT a physician or surgeon. Even if he were interested, he does not and cannot do surgery in people. He cannot develop this technique for human.


  2. #12
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    Quote Originally Posted by Wise Young View Post

    John Martin is a basic scientist. He is NOT a physician or surgeon. Even if he were interested, he does not and cannot do surgery in people. He cannot develop this technique for human.

    DR. young, I realize John Martin is NOT a surgeon, My thought was to try and understand where his animal research was and to try and find a surgeon experienced in nerve rerouting to take a look at this process and try and help move it to the translational phase when it's ready. I'm impatient, I want to move things along and progress so maybe some level of recovery might be realized by my 20 year old son in his lifetime.


  3. #13
    Quote Originally Posted by rjames View Post
    DR. young, I realize John Martin is NOT a surgeon, My thought was to try and understand where his animal research was and to try and find a surgeon experienced in nerve rerouting to take a look at this process and try and help move it to the translational phase when it's ready. I'm impatient, I want to move things along and progress so maybe some level of recovery might be realized by my 20 year old son in his lifetime.

    Rick, I was sitting in the audience with a very good neurosurgeon (Justin Brown) from Washington University in St. Louis, listening to John Martin speak and getting excited about the work. Martin was doing was he should have been doing, talking to clinicians about his work and training clinicians in his laboratory.

    Advancing surgical practice is even slower than drugs or other types of therapies. This is because it must be taught, often person-to-person, in the operating rooms. That is one of the reasons why peripheral nerve bridging has not caught on yet in the United States. It is because so few neurosurgeons were trained to do such nerve grafts.

    Please understand that I was Director of Neurosurgery Research at NYU/Bellevue Medical Center for 20 years. During that period, most of the residents spent time in my laboratory. But, in the end, after spending 20 years trying to change neurosurgical practice, I realized that I was not having much impact on neurosurgery of spinal cord injury.

    Even in China, dissemination of surgical procedures is very slow and frustrating. So, for example, while there are individual surgeons with very substantial experience using peripheral nerves to graft one part of the nervous system to another, it is not yet practiced widely. Surgical techniques are being taught one-on-one in an apprentice-style approach.

    One of the most important functions of the ChinaSCINet is that it has gotten many of the surgeons who do spinal surgery together in regular workshops and meetings. I believe that this has markedly speeded up transfer of surgical approaches from center to center. Since 2004, for example, three other centers besides Hongyun Huang's group, had tried OEG cells.

    Having a network disseminate the treatment techniques is one of the most efficient ways of advancing surgical practices.


  4. #14
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    I wanted to bring this thread up again based on the recent nerve grafting work ans successes published by Dr. Jerry Silvers group at Case Western.

    I think this approach could be translated to humans quicker than about anything out there. How do we rally behind it? I have traded a few more emails with Dr. John Martin over the past few years and he has moved his research into larger animals (Cats and Pigs I think) and is awaiting his paper to be published.

    It would be nice if we could get all the experts in this area to collaborate and devise a plan to move this type of research along quickly to the clinic.

  5. #15
    This interview was posted September 2007 by Beth29 when Dr. Silver first announced his intention to try to build the bridge to restore breathing.

    Silver 'breathes' new life in turning HOPE into REALITY
    In wanting to do what I could financially for spinal cord research I looked into which local organization was the best for advancement in research and I found Dr. Jerry Silver, Ph.D. at Case Western Reserve University. This resulted in a chance to meet with him one on one and learn about his accomplishments and direction.

    "I want to help people breathe"

    "I want to help people breathe", he said and this is prominent in Dr. Silver's mind. He is determined to make it happen. There is light at the end of the tunnel and momentum is building.

    Dr. Silver's research doesn't require stem cell research. And it doesn't require cyclosporine since he utilizes the patients own internal parts. Cyclosporine is used to reduce organ transplant rejection. He utilizes an autograft which uses one part of the patient's body in a different location; therefore their immune system doesn't reject the graft.

    In short, he builds a bridge to connect part of the spinal cord above the injury to the corresponding part of the spinal cord below the injury. I created the visual aides below after watching Dr. Silver's presentation. Their tests have been conducted on the front paw of rats and moved to testing respiratory improvements.

    They call it a bridge because it simply bridges the gap. Like a bridge over water or you can think of it like a bypass on a highway when they do construction on the main road. Dr. Silver explained that the bridge is made by using a segment of the patient's own peripheral nerve (there are thousands of these in the body). They choose one where the loss of a small segment of a nerve it not too detrimental. Typically they use a piece of the sural nerve or intercostal nerve where the resulting loss of function (mostly sensation) is not critical. An autograft is the term used to describe the action of moving this segment of the peripheral nerve to where it will be utilized.

    To restore foot function in hemisected rats (only half the spinal cord affected) they use a nerve autograft plus an enzyme. An injured rat breathes shallower and faster, like a panting dog. Thus far for breathing they have only used the enzyme to stimulate nerve sprouting from the remaining side of the spinal cord to restore breathing capacity to 90% within 8 weeks of injury. The volume per breath increased and the frequency slowed down.

    Dr. Silver would like to use the full treatment (autograft & enzyme) for breathing in the future so they can get closer to 100% return of function. His associate, Warren Alilain has written and submitted an abstract for the Society for Neuroscience and they will be attending the annual meeting in November. An abstract, in the science world, is a very brief summary or excerpt to a longer publication. And the scientists can read the abstracts and decide which meetings and topics to attend at the event.

    My hope is that orthopedic surgeons, neurosurgeons, and urologists can apply Dr. Silver's findings to assist in re-acclimating partial if not full function to hands, bladders, bowels, and legs to those in need.

    At the end of his presentation I had a few questions for Dr. Silver.

    Q: You know which nerves you are directing into the bridge, but does the body know what to hook them up to when you stick the other end of the bridge into the spinal cord below the injury?

    A: That's a good question. They go to where they're needed. They don't go very far. They don't go up and down. And we're targeting the end of the bridge to the place in the spinal cord we know is controlling breathing. If you get fibers to grow without a bridge you don't know where they're going to go. Our bridge lets us target the nerve fibers for a specific place.

    Q: Since you're ready to move onto primates, do you have an idea how long? Could it be another 10 years on primates?

    A: No, if we could show we can bring back hand function, that's the model in California, a C-5 lesion with just the enzyme trying to get fibers on the other side of the spinal cord to help move the hand. Right now it's very slow it doesn't work and we're going to add the enzyme and we have a few other tricks to do. If a primate that uses his hand like we do can improve markedly, I see no reason why we couldn't jump to human almost instantly.

    Q: Okay so it could be 3-4 years away.

    A: Maybe even sooner. The primate trials begin this year or next year and it could take just a year or two. As soon as we can show that the hand function in a primate is remarkably improved by simply injecting a tiny little needle, I don't see why some neurosurgeon might write a IRB and find a couple of patients that are willing to do this since we do no harm by a simple injection. Now building a bridge is another issue because - that - you have to have a surgery.

    So yeah, we would move to primates and go to human. We're as close to going to human as we've ever been with this kind of success and no one else is getting it around the world - we're doing pretty good. Nothing fancy, just an enzyme and a bridge and it's taken over 20 years to get this far.

    A little bit of background: When a doctor writes an IRB he is actually writing a proposal to his hospital requesting permission to do something specific such as using Dr. Silver's technique on his human patients. This proposal is reviewed by the hospital's Internal Review Board that the doctor works for (thus the name, IRB). Depending on the protocols it may require FDA approval but the details of that are beyond the purpose of this posting at this time.

    Q: How can the regular person help you?

    A: Like you? (yeah, like me - what can I do). It depends on how aggressive and proactive you are and who you want to talk to. We're presenting this data; it's now on-line in an abstract at the Society for Neuroscience meeting. It may garnish some attention when presented at the meeting.

    Q: How does this relate to chronic situations?

    A: All of our work is in acute animals. Dr. John Houle, my partner, (Drexel University) and former student Dr. Veronica Tom are working on chronic. There is no obvious reason why it wouldn't work. For them, they make lesion and wait six months and then put in a bridge and they're doing that now. There is hope for chronic.

    This is not cure but incremental improvement.
    It's just a foot but that translates to use of a hand.
    Not walking, you're not gonna get up and run away or play piano.
    As you saw in our presentation, the movements in the rat were kind of sluggish but enough to keep it up on a running wheel.

    This is one small step for rat, one giant leap for mankind.

    Q: Thank you Dr. Silver.

    A: My pleasure

    How this respiratory testing will relate to humans with spinal cord injuries that affect that area for them is as follows. With all spinal cord injuries it is a case by case situation with how severe and bi-lateral the effects are. Basically, an incomplete injury could benefit from just the enzyme treatment. In cases of complete injury (such as the case with Christopher Reeves) a bridge would be required. At this time bridges have not been used in respiratory subjects and that is the direction Dr. Silver's work is headed.

    Having spoken with Dr. Silver since our meeting, I've learned that one of his former students is working with Dr. John Kaas at Vanderbilt University in Tennessee. They have begun the hand model testing on monkeys using the same technique Dr. Silver has used on rats.

    From that very short phone conversation, I got the sense that the debates and discussions Dr. Silver expects to have will be related to distance issues - the length of the bridges needed to cover the lesions going from C2 to C4 for things such as respiratory issues and going from C5 to C8 for hand functions. These distances are not so far and he is confident the length will not be a significant factor. It certainly is a variable to be weighed and overcome but it shouldn't be a significant factor.

    The other issue will be chronic situations. It is yet to be seen if there have been changes in how the nerve fibers communicate with each other below lesions as time has passed. And, if there are changes how that will effect introducing a bridge to the situation. We do know that dormant nerves are capable of being revived.

    I've enjoyed talking with Dr. Silver immensely.
    I've learned a lot from him and he is doing incredible things!
    Last edited by GRAMMY; 07-17-2011 at 07:17 PM.

  6. #16
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    Grammy, thanks for posting that article. They talked about primate testing almost 4 years ago....wonder how that turned out?

    I really believe in this bridging approach, i hope it does not turn into another research success study that turns Into a "Shelved" project collecting dust in some file cabinet...


  7. #17
    Rick, I'll see if I can find out specifically what changes took place over the past 4 years or so to get them where they are today. I'd like to know more also. I'm sure it hasn't been a "straight" shot. Dr. Silvers work goes back for many many years. None of his work has been shelved so far, it's been pushed and expanded further each year and with each discovery. He's not a newcomer to the chronic sci therapy field. He's had a successful career and really pushed the science forward for us. He has genuine history. I do know Dr. John Kaas at Vanderbilt had been working with primates and arm function work for years prior to this interview.
    Last edited by GRAMMY; 07-17-2011 at 09:17 PM.

  8. #18
    Just finally reading these later responses after a couple years.

    Couldn't agree more!

    I met with every top neurosurgeon (for Brachial Plexus Injury and avulsion) I could get my hands on here in the US (Harvard, Standard, UCLA, USC, Dartmouth, Columbia, NYU, Duke, Mayo, LSU, etc) and went abroad to the UK and met some there (Dr Thomas Carstedt, great surgeon/innovator and wonderful person). It was nearly impossible to convince American neurosurgeons that techniques in Europe, India, China and elsewhere where any more advanced than what was happening here in the US.

    Very frustrating indeed! And I thought losing my right arm was bad... I can only imagine what it'd be like being Director of Neurosurgery Research for 20 years!

    Thank you Dr Young for all you do!!!

    Eternally grateful.


    Quote Originally Posted by Wise Young View Post


    Finally, I want to point out that Martin himself will not be doing surgery on patients. There is much confusion about what a scientist does and a clinician does. The surgery has to be done by a neurosurgeon. The block is at the translation step. Part of the problem that you refer to is not a problem with scientists not doing their work. The problem is that there is no method of translating basic science into clinical practice. There are too few neurosurgeons who are committed, who keep up with the research, and who are willing to spend the time and risk to move such techniques into the clinic. At least in the United States, there is almost no incentive for a neurosurgeon to do anything new and a lot of disincentives for the neurosurgeons to do anything risky. I am spending a lot of time bring individual surgeons and rehabilitation doctors to China, for example, to show them. Many won't believe until they see with their own eyes.

    A lot of this should change as we get more clinical trials going in the United States. We have had so few clinical trials in the United States over the past decade that doctors get use to practicing without clinical trials. In short, we have just created another generation of doctors who are not used to spinal cord injury clinical trials.


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