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Thread: Working2Walk 2011 features Dr. Jerry Silver!

  1. #11
    Quote Originally Posted by jsilver View Post
    They have been hesitant to move forward with a bridge building + ch'ase clinical trial in people with very high injuries for fear of doing more damage.
    I understand the caution, but I know I for one would risk it. 12 suctions today and counting. Just surviving takes a toll.
    Last edited by Scaper1; 10-29-2011 at 08:40 PM.

  2. #12
    Quote Originally Posted by jsilver View Post
    If you watched the video, you saw and heard 2 more important pieces of the puzzle. the most important is the very last bit where we show a strong return of function in the respiratory system in animals that had sustaing a cord lesion 1 year earlier. Recovery occurs rapidly (within 1 week) with a single injection of enzyme. Importantly the return of function at chronic time points is even stronger than the effect we see at acute stages. If you're interested we can begin to discuss various experiments that we have done which have helped us to begin to understand why this should be. the results are very exciting and are relevant to all treatments (including the use of stem cells) that target chronic injury. Hopefully , this new work will strongly stimulate Acorda to get going with a chondroitinase clinical trial. Secondly, I showed new work where we completely transected the cord and built a bridge across the gap. here we focused on the return of bladder function that continued to improve nicely at around 6 months following treatment. In the case of complete transection injuries we need to build a bridge and our new work shows that for the urinary system, at least, we can surely restore a good measure of function. By the way If you look carefully at one of the slides you may notice that I also describe a nice improvement in locomotor function in these same animals from a BBB score of 2 to a score of 7, a 5 point increase. However, I need to stress that a score of 7 is far from normal walking but there is improvement (I didn't stress walking in my talk) Thus, if we wait long enough regenerating axons can travel relatively long distances in the spinal cord and hook up synaptically to restore certain critical functions. I'm hoping that a courageous team of neurosurgeons in our country joins me in attempting a clinical trial in people with cord injuries below the respiratory nuclei. They have been hesitant to move forward with a bridge building + ch'ase clinical trial in people with very high injuries for fear of doing more damage. There's is not much left working is high quads. By the way Henrich Cheng in Taiwan has already attempted many such surgeries in humans so this procedure is certainly feasible in humans. He has yet to combine bridging +ch'ase.
    Dr. Silver, How does the nerve graft restore sensation to the restored function?

  3. #13
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    Quote Originally Posted by jsilver View Post
    If you watched the video, you saw and heard 2 more important pieces of the puzzle. the most important is the very last bit where we show a strong return of function in the respiratory system in animals that had sustaing a cord lesion 1 year earlier. Recovery occurs rapidly (within 1 week) with a single injection of enzyme. Importantly the return of function at chronic time points is even stronger than the effect we see at acute stages. If you're interested we can begin to discuss various experiments that we have done which have helped us to begin to understand why this should be. the results are very exciting and are relevant to all treatments (including the use of stem cells) that target chronic injury. Hopefully , this new work will strongly stimulate Acorda to get going with a chondroitinase clinical trial. Secondly, I showed new work where we completely transected the cord and built a bridge across the gap. here we focused on the return of bladder function that continued to improve nicely at around 6 months following treatment. In the case of complete transection injuries we need to build a bridge and our new work shows that for the urinary system, at least, we can surely restore a good measure of function. By the way If you look carefully at one of the slides you may notice that I also describe a nice improvement in locomotor function in these same animals from a BBB score of 2 to a score of 7, a 5 point increase. However, I need to stress that a score of 7 is far from normal walking but there is improvement (I didn't stress walking in my talk) Thus, if we wait long enough regenerating axons can travel relatively long distances in the spinal cord and hook up synaptically to restore certain critical functions. I'm hoping that a courageous team of neurosurgeons in our country joins me in attempting a clinical trial in people with cord injuries below the respiratory nuclei. They have been hesitant to move forward with a bridge building + ch'ase clinical trial in people with very high injuries for fear of doing more damage. There's is not much left working is high quads. By the way Henrich Cheng in Taiwan has already attempted many such surgeries in humans so this procedure is certainly feasible in humans. He has yet to combine bridging +ch'ase.
    Dr. Silver,
    Yes I certainly would like to discuss/learn more about the various studies you have done to better understand why there has been such success with Chronic injuries versus Acute injuries. I think I speak for everyone on this board when I say we are all VERY interested in Chronic therapies.

    I totally understand the risk in bridging higher injuries but I'm sure there are some high level Quads that would be willing to take some risk for a possibility of getting off a ventilator. I would think it would make more sense to start with Thoracic injuries and work towards restoring Bladder and Bowel, perfecting that treatment and then move to high level quads.

    I did watch your W2W video and listened to the end where you were talking about the successes you were seeing in chronic injuries, that's what has me so excited. I have been digging around the research about nerve grafting (Periferal) for a couple years and have thought it might be the way to go, making a "Patch Cord" to by pass the injury and with your successes it seems like my hunch was correct. Dr. John Martin is doing something similar to you but using nerve roots but not have quite as much success, Maybe he needs chondroitinase. I also heard the part about walking but i figure it"s just a matter of time before you figure that out too.

    As you mentioned there are surgeons that have been doing nerve grafting for years and I would think they could learn this type of procedure pretty quickly.

    How can our SCI community help you take your work to an available treatment? I would hate to see you retire (LOL) before this is realized....

  4. #14
    please, some of us want to walk more than anything else

    that is one trouble with us with sci; we all seem to want different things, partly due to our different injuries

  5. #15
    Quote Originally Posted by rjames View Post
    Dr. Silver,
    Yes I certainly would like to discuss/learn more about the various studies you have done to better understand why there has been such success with Chronic injuries versus Acute injuries. I think I speak for everyone on this board when I say we are all VERY interested in Chronic therapies.

    I totally understand the risk in bridging higher injuries but I'm sure there are some high level Quads that would be willing to take some risk for a possibility of getting off a ventilator. I would think it would make more sense to start with Thoracic injuries and work towards restoring Bladder and Bowel, perfecting that treatment and then move to high level quads.

    I did watch your W2W video and listened to the end where you were talking about the successes you were seeing in chronic injuries, that's what has me so excited. I have been digging around the research about nerve grafting (Periferal) for a couple years and have thought it might be the way to go, making a "Patch Cord" to by pass the injury and with your successes it seems like my hunch was correct. Dr. John Martin is doing something similar to you but using nerve roots but not have quite as much success, Maybe he needs chondroitinase. I also heard the part about walking but i figure it"s just a matter of time before you figure that out too.

    As you mentioned there are surgeons that have been doing nerve grafting for years and I would think they could learn this type of procedure pretty quickly.

    How can our SCI community help you take your work to an available treatment? I would hate to see you retire (LOL) before this is realized....
    @rjames: Did you see the chondroitinase video that was uploaded just before Dr. Silver's? http://www.unite2fightparalysis.org/video_library__1

  6. #16
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    Hey, all I have ever wanted in almost 3 decades of this crap is my bladder back, but how can anyone not agree that vent dependence should be solved first?!

    Imagine the freedom of not depending on a vent with all its 'probability' of error with pop-offs, mucous suctions, power failures and human errors (I wonder if suctioning would still happen because you would need the ability to cough?)
    Roses are red. Tacos are enjoyable. Don't blame immigrants, because you're unemployable.

    T-11 Flaccid Paraplegic due to TM July 1985 @ age 12

  7. #17
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    Quote Originally Posted by GRAMMY View Post
    @rjames: Did you see the chondroitinase video that was uploaded just before Dr. Silver's? http://www.unite2fightparalysis.org/video_library__1
    Hi Chris,
    No I haven't had a chance to watch all the videos yet, only Dr. Silvers. I will try to watch the one in the link you provided when I get home tomorrow. Thanks for pointing that one out to me....

    Rick

  8. #18
    jsilver, what was the reason that Mother-Nature have chosen to wrap PNS nerves in Schwann cell-formed myelin and for CNS ones have decided that oligodendrocytes is more suitable material, are there any reasonable explanation to this?
    You have assessed Paul Tesar's findings on oligo as a "good thing", what sci-models will benefit from it where Schwann cells are in no way do the job?
    Last edited by kivi66; 10-30-2011 at 02:17 PM.

  9. #19
    Quote Originally Posted by rjames View Post
    Dr. Silver,
    Yes I certainly would like to discuss/learn more about the various studies you have done to better understand why there has been such success with Chronic injuries versus Acute injuries. I think I speak for everyone on this board when I say we are all VERY interested in Chronic therapies.

    I totally understand the risk in bridging higher injuries but I'm sure there are some high level Quads that would be willing to take some risk for a possibility of getting off a ventilator. I would think it would make more sense to start with Thoracic injuries and work towards restoring Bladder and Bowel, perfecting that treatment and then move to high level quads.

    I did watch your W2W video and listened to the end where you were talking about the successes you were seeing in chronic injuries, that's what has me so excited. I have been digging around the research about nerve grafting (Periferal) for a couple years and have thought it might be the way to go, making a "Patch Cord" to by pass the injury and with your successes it seems like my hunch was correct. Dr. John Martin is doing something similar to you but using nerve roots but not have quite as much success, Maybe he needs chondroitinase. I also heard the part about walking but i figure it"s just a matter of time before you figure that out too.

    As you mentioned there are surgeons that have been doing nerve grafting for years and I would think they could learn this type of procedure pretty quickly.

    How can our SCI community help you take your work to an available treatment? I would hate to see you retire (LOL) before this is realized....

    I awoke this morning to lots of questions, so let me take one at a time. The experimental results I reported at W2W on our one year chronic animals is in its early phases. However, we have seen good functional recovery in the respiratory system following an incomplete lesion at C2 in every animal. So I think the results are going to hold up. But why should this be? Why is functional recovery after chondroitinase injection more robust after chronic stages than after acute? Why is recovery so rapid (just 1 week)? Is this result in the respiratory motor system representative of what might also be possible in other systems (such as locomotor, bowel, bladder sexual function)? An answer to this question comes from experiments that we are conducting on the acutely and now chronically injured spinal cord using a technique called optogenetics (See a paper in J Neuroscience by Alilain et al. and just Google some key words "Light induced rescue of breathing after spinal cord injury"). Briefly, after spinal cord injury we inject a virus that carries a light sensitive protein called channel rhodopsin into the region of the phrenic motor neurons and their associated interneurons. This allows us to turn on an entire circuit of neurons and watch what the output is. At acute stages after injury the technique allowed us to briefly restore NORMAL breathing quite remarkably to the paralyzed hemidiaphragm. HOWEVER, AFTER CHRONIC STAGES FOLLOWING INJURY (3 MONTHS OR MORE), TURNING ON THE RESPIRATORY CIRCUITRY WITH LIGHT LEAD TO VERY VERY STRONG BUT TOTALLY CHAOTIC BREATHING ON BOTH SIDES OF THE DIAPHRAGM THAT RESULTED IN MUCH WORSE (INDEED, DEADLY) FUNCTION. The remaining good lung was now totally screwed. This tells us that over protracted periods of time following SCI there is a slow plasticity with formation of new connections at and below the level of the lesion. However, these connections are BAD and nature works hard to cover them up with proteoglycan containing net so there is no further loss of function. The very good news is that with the help of the chrondroitinase enzyme, the new and exuberant circuitry can reform itself quickly and produce a very strong output that now becomes patterned. Does this same sort of bizarre plasticity occur in the locomotor system. Indeed, Greqoire Courtine has shown something identical in the development of what he calls "chaotic" walking behaviors to what we are seeing in the respiratory system. Importantly, he has shown that this untoward locomotor plasticity at chronic stages following SCI (again in rats) can be sculpted into more normal walking patterns with a tremendous amount of robotic training, beyond what any human could tolerate. You see, nature is continually trying to inhibit any and all new synapses that rehab training is creating, even the good ones. SO, FOR ALL THOSE INDIVIDUALS AT ANY LENGTH OF TIME PAST THE INJURY AND WITH ANY REMAINING DESCENDING INPUTS THAT CAN ALLOW SOME LEVEL OF SUPRASPINAL CONTROL PAST THE LESION, WE NEED TO TEST THE EFFICACY OF COMBINING TRAINING WITH CHONDROTINASE. These experiments should occur first in animal models and that is precisely what we need to do next for the respiratory system. Courtine is doing these experiments for walking. My guess is that in some individuals, the rapid return of function via the use of stem cells (like the guy now being publicized in the Brazil trial) also involves modification of the proteoglycan containing net. I would love to see what happens to the net in the presence of stem cells. I'll bet it becomes reduced somewhat (we need stem cells plus ch'ase). For those with totally complete lesions we will need to use a bridging strategy. I hope this answers some of your questions but if not please ask more. I will come back later today and continue our discussion.

  10. #20
    Quote Originally Posted by kivi66 View Post
    jsilver, what was the reason that Mother-Nature have chosen to wrap PNS nerves in Schwann cell-formed myelin and for CNS ones have decided that oligodendrocytes is more suitable material, are there any reasonable explanation to this?
    You have assessed Paul Tesar's findings on oligo as a "good thing", what sci-models will benefit from it where Schwann cells are in no way do the job?
    Well, nobody really knows the answer to this. Schwann cells and astrocytes do not mix with each other at all. In addition, Schwann cells make what is known as a basal lamina, a tenacious membrane between astrocytes or fibroblasts. The Schwann cell basal lamina around peripheral axons is in the form of tubes (called Bands of Bungner) and are a major reason why PNS axons can regenerate along Schwann cells. It is likely that basal lamina in the CNS is not desirable because in gray mater this would markedly interfere with synapse formation. Oligodendrocytes can myelinate many axons but Schwann cells tend to myelinate just one at a time.

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