Announcement

Collapse
No announcement yet.

Working2Walk 2011 features Dr. Jerry Silver!

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

    #16
    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

    Comment


      #17
      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

      Comment


        #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; 30 Oct 2011, 2:17 PM.

        Comment


          #19
          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.

          Comment


            #20
            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.

            Comment


              #21
              Dr. Silver,
              I didn't mean for you to wake up on Sunday morning barraged with a bunch of questions but thank you for responses to my question although they take me some time to digest due to my limited understanding of SCI research, but I'm learning....

              It's very exciting and uplifting knowing there are dedicated people like yourself (and others I need to ad) using a lifetimes worth of work/knowledge and making the progress you are towards a fix for this injury.

              I don't want to bog you down with a bunch more questions because I know you have much more important work ahead of you but I do appreciate you coming here and filling us in on your works progress, we are all eager for that news, so please continue to do that.

              Keep up the great work you are doing and I'm sure I will read shortly that you have figured out a graft that will help walking.......

              Rick James

              Comment


                #22
                Dear rjames,

                Please, don't hesitate to ask lots of questions. I am truly grateful to those who seek answers and knowledge about SCI. Asking questions helps brings out the truth about how close we really are to helping people with SCI regain function.

                In regards to the use of bridging strategies to build a roadway for regeneration, there are a huge number of different approaches. In general, every single approach, including the use of stem/progenitor cells, biopolymers and even segments of peripheral nerves alone tend to allow regenerative growth into but not beyond the graft. We have chosen the peripheral nerve autograft +chondroitinase for a number of reasons. Mother Nature has engineered the peripheral nerve over millions of years to be the most perfect regeneration bridge , so why not take advantage of her efforts. She just needed a little help when it came to transplanting the regenerative potential of the PNS into the CNS in order to get some axons out of the bridge. Our work with this technique to restore respiration after cord hemisection, has demonstrated that a profound amount of breathing recovery can occur when we do things right. We are now perfecting techniques to improve upon this strategy for other systems and in animals with cord lesion that are much larger. We anticipate the use of 2 bridges for the potential restoration via regeneration of crude hand function and I showed at W2W our ongoing studies to restore urinary function after complete transection injury. Now the question remains as to whether neurosurgeons will apply these strategies to humans. For those with high cervical lesions we will need to be especially cautious that the technique does no more harm. So I think we will need to demonstrate the efficacy of the technique in a larger animal model. For those with lower injuries the chances of additional damage are mitigated by the lower position of the lesion, so surgeons may be more willing to operate. We just need to keep going full speed and publish very high quality papers. If we do this only good things can follow but I need to stress that walking is one of the more difficult hurdles to overcome. i envision a collaborative effort between the FES people (such as Reggie Edgerton/Susan Harkema) and us biological regenerators to maximize walking potential.

                Comment


                  #23
                  Chase and bridging is a one shot therapy? Or could be used more than once to improve even more (3-4 years before the first therapy for example)?
                  -Ramps in buildings are necessary, but it would be usefull to have another ones for people (mind/heart).....

                  -Hoc non pereo habebo fortior me

                  Comment


                    #24
                    Dr. Silver,

                    We often group bladder, bowel and sexual function together like it's one thing. Can you offer your opinion on lumping these functions together as it relates to your approach to improving urinary function?

                    Asked more directly, does your technique restore/improve bowel and sexual function along with bladder function?

                    Comment


                      #25
                      Good question by quadfather

                      Comment


                        #26
                        Originally Posted by kivi66
                        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.

                        jsilver, what about the second question?

                        Comment


                          #27
                          Originally posted by Isildur View Post
                          Chase and bridging is a one shot therapy? Or could be used more than once to improve even more (3-4 years before the first therapy for example)?

                          If we do this right the first time there should be no need to re-enter the spinal cord for repeated injections of the enzyme. Also this would not be desirable.

                          Comment


                            #28
                            Originally posted by quadfather View Post
                            Dr. Silver,

                            We often group bladder, bowel and sexual function together like it's one thing. Can you offer your opinion on lumping these functions together as it relates to your approach to improving urinary function?

                            Asked more directly, does your technique restore/improve bowel and sexual function along with bladder function?
                            We have not examined bowel or sexual function although bowel function is in part controlled by the same neurons that control the bladder.

                            Comment


                              #29
                              Dr. Silver,

                              I wonder how you think stem cells and chase would be best administered. Would they be injected concurrently, or would chase be administered prior to the stem cells in order to clear out the CSPG. Also, would injecting these therapies simultaneously affect the dosage available for either therapy due to the limitation on injection volume?

                              Thanks for taking the time to answer these questions.

                              Comment


                                #30
                                Originally posted by jsilver View Post
                                Dear rjames,

                                Please, don't hesitate to ask lots of questions. I am truly grateful to those who seek answers and knowledge about SCI. Asking questions helps brings out the truth about how close we really are to helping people with SCI regain function.

                                In regards to the use of bridging strategies to build a roadway for regeneration, there are a huge number of different approaches. In general, every single approach, including the use of stem/progenitor cells, biopolymers and even segments of peripheral nerves alone tend to allow regenerative growth into but not beyond the graft. We have chosen the peripheral nerve autograft +chondroitinase for a number of reasons. Mother Nature has engineered the peripheral nerve over millions of years to be the most perfect regeneration bridge , so why not take advantage of her efforts. She just needed a little help when it came to transplanting the regenerative potential of the PNS into the CNS in order to get some axons out of the bridge. Our work with this technique to restore respiration after cord hemisection, has demonstrated that a profound amount of breathing recovery can occur when we do things right. We are now perfecting techniques to improve upon this strategy for other systems and in animals with cord lesion that are much larger. We anticipate the use of 2 bridges for the potential restoration via regeneration of crude hand function and I showed at W2W our ongoing studies to restore urinary function after complete transection injury. Now the question remains as to whether neurosurgeons will apply these strategies to humans. For those with high cervical lesions we will need to be especially cautious that the technique does no more harm. So I think we will need to demonstrate the efficacy of the technique in a larger animal model. For those with lower injuries the chances of additional damage are mitigated by the lower position of the lesion, so surgeons may be more willing to operate. We just need to keep going full speed and publish very high quality papers. If we do this only good things can follow but I need to stress that walking is one of the more difficult hurdles to overcome. i envision a collaborative effort between the FES people (such as Reggie Edgerton/Susan Harkema) and us biological regenerators to maximize walking potential.
                                Do you think the FES would mainly be used to retrain the walking motion and build up muscle and then dispensed with? Or are you proposing some sort of hybrid system? I thought the central pattern generator meant that very little spinal cord was needed to enable good walking?

                                Comment

                                Working...
                                X