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    Jerry Silver update

    Possible good news for chronic's

    https://www.sciencedaily.com/release...1127131559.htm

    #2
    Yea. Heading in the right direction. Thank you Dr. Silver and his team!!

    Comment


      #3
      Originally posted by 6 Shooter View Post
      Yea. Heading in the right direction. Thank you Dr. Silver and his team!!
      If you have any questions about our new work then please just ask and I will do my best to answer.

      Here is a link to the paper for all to read. it is open access. "Rapid and robust restoration of breathing long after spinal cord injury"

      https://www.nature.com/articles/s41467-018-06937-0

      Comment


        #4
        the golden question is: "approxamitely how long until human trials commence"

        EDIT: big congratulations and appreciation for you and your teams work
        "That's not smog! It's SMUG!! " - randy marsh, southpark

        "what???? , you don't 'all' wear a poop sac?.... DAMNIT BONNIE, YOU LIED TO ME ABOUT THE POOP SAC!!!! "


        2010 SCINet Clinical Trial Support Squad Member
        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


          #5
          Jerry will your therapy cure bladder bowel sexual function in chronic lumbar injury patients too? When starting trial and will you take lumbar injury patients in trials?

          Comment


            #6
            Originally posted by jsilver View Post
            If you have any questions about our new work then please just ask and I will do my best to answer.

            Here is a link to the paper for all to read. it is open access. "Rapid and robust restoration of breathing long after spinal cord injury"

            https://www.nature.com/articles/s41467-018-06937-0

            Keep up with this fantastic work, Jerry.
            No one ever became unsuccessful by helping others out

            Comment


              #7
              "Similar to locomotor training, acute repetitive intermittent hypoxia (IH) conditioning can facilitate a small, transient gain in respiratory function following sub-chronic SCI."

              Could be an intermittent hypoxia regimen mimicked using hypoxia inducible factors or, better, HIF prolyl-hydroxylase inibitors (FG-4592, BAY-853934)?
              T4 AIS A since 07/05/2017

              "We lie the best when we lie to ourselves."

              Comment


                #8
                Interesting reading for a C3 vent dependent quad. Is build up of secretions still a problem? I'd love to get rid of vent and trache, when can I volunteer for a trial?

                Comment


                  #9
                  Originally posted by jsilver View Post
                  If you have any questions about our new work then please just ask and I will do my best to answer.

                  Here is a link to the paper for all to read. it is open access. "Rapid and robust restoration of breathing long after spinal cord injury"

                  https://www.nature.com/articles/s41467-018-06937-0
                  Is there anything that we can do to help with the process moving forward?

                  Comment


                    #10
                    Yes Dr. Silver

                    Human trials??? Especially hand function.

                    Comment


                      #11
                      Dr. Silver--would you please provide a simple explanation as to why ChABC, when injected below the level of injury, tends to encourage neurons and axions to penetrate the glial scar tissue and reconnect below. In the past, you have mentioned that the glial scar is quite a formidable barrier. Also, am wondering if injecting above and below the injury site would amplify the current positive results you are seeing in the lab.

                      Comment


                        #12
                        Originally posted by 6 Shooter View Post
                        Dr. Silver--would you please provide a simple explanation as to why ChABC, when injected below the level of injury, tends to encourage neurons and axions to penetrate the glial scar tissue and reconnect below. In the past, you have mentioned that the glial scar is quite a formidable barrier. Also, am wondering if injecting above and below the injury site would amplify the current positive results you are seeing in the lab.

                        Thanks for the question. We were not actually targeting the scar that surrounds the lesion, which was made at cervical level 2. We were targeting the so-called perineuronal net (PNN), a cocoon-like matrix structure made of proteoglycans that surrounds the connections that occur between neurons, called synapses. It was previously thought that one of the major functions of the perineuronal net was to stabilize synapses but, in doing so, prevents sprouting of new connections. We have discovered during our work that the net actually functions also to block the activity of newly regenerating connections that are forming very slowly below the level of the lesion in the spinal cord. In simple terms, over time, the spinal cord tries very hard to fix the paralysis that occurs after spinal cord injury by expanding (ie., sprouting) the axonal arbor of special types of interneurons that can amplify the much reduced signals coming from above (ie., those few that are spared after the injury). There is also a very slow sprouting of spared axons of the serotonergic system below the level of injury which is also a way of amplifying the signals from above. But the most bizarre thing happens --- instead of allowing this sprouting to occur readily, the spinal cord instead increases (rather than decreases) the density of the inhibitory proteoglycans in the perineuronal net which not only slows down the sprouting but, surprisingly, blocks synaptic transmission. So the new connections can't even work once they have sprouted. Indeed, the harder one works to use rehabilitative training to improve recovery the thicker the net becomes. It's formation is activity dependent. Therefore, we injected the enzyme farther down the spinal cord at the level of C4-5 to remove the net around the motor nerve cells that receive the newly sprouted amplifying connections from the local interneurons and serotonergic system. In turn, the motor neurons send their axons out to the muscles (we targeted motor neurons that go out to the diaphragm and upper forearm). The results were amazing with full and rapid recovery after a near lifetime of paralysis. We think this fast recovery is due to the enzyme unmasking the new connections that had already formed over time. Thus, the longer the time after injury the better was the recovery. One important caveat is that when we pushed respiratory rehab too hard in combination with the enzyme ( a strategy called acute intermittent hypoxia) then in some animals, instead of getting nicely patterned respiratory functional recovery, a debilitating chaotic activity developed. We learned that this unwanted activity occurred because the combo strategy caused too much serotonergic sprouting. So we now have to work out what the optimal strategy is to maximize the speed and amount of recovery.

                        Comment


                          #13
                          Dr. Silver, this is fascinating. I've rented equipment from hypoxico.com that let me do two 2-week sessions of acute hypoxic therapy with my home health care aides and it took me a while to realize I wasn't doing it quite right and then I burned a small hole in the hose. It did help my legs move faster for a while. I wish I had better instructions so I could get better results next time. I was using a walker and briefly walking then. Now after two falls and no 4-AP use, I'm barely standing...

                          Comment


                            #14
                            Dr. Silver, all the respect and appreciation for your dedication and the amazing work you’re conducting in order to hopefully help us some day, the sooner the less suffering and hardship we’ll have to endure.
                            That’s why I have to raise the golden question again, as this is what it’s all about, when can we approximately see, The Human Trials?
                            I’m aware that it might still be a long way until it happens, but it would still be great to know that they will happen at some point. Please give a rough estimate on plans for future trials. I do also apologise if the question was too forward.
                            Thank you very much Dr. Silver.

                            Comment


                              #15
                              Originally posted by jsilver View Post
                              Thanks for the question. We were not actually targeting the scar that surrounds the lesion, which was made at cervical level 2. We were targeting the so-called perineuronal net (PNN), a cocoon-like matrix structure made of proteoglycans that surrounds the connections that occur between neurons, called synapses. It was previously thought that one of the major functions of the perineuronal net was to stabilize synapses but, in doing so, prevents sprouting of new connections. We have discovered during our work that the net actually functions also to block the activity of newly regenerating connections that are forming very slowly below the level of the lesion in the spinal cord. In simple terms, over time, the spinal cord tries very hard to fix the paralysis that occurs after spinal cord injury by expanding (ie., sprouting) the axonal arbor of special types of interneurons that can amplify the much reduced signals coming from above (ie., those few that are spared after the injury). There is also a very slow sprouting of spared axons of the serotonergic system below the level of injury which is also a way of amplifying the signals from above. But the most bizarre thing happens --- instead of allowing this sprouting to occur readily, the spinal cord instead increases (rather than decreases) the density of the inhibitory proteoglycans in the perineuronal net which not only slows down the sprouting but, surprisingly, blocks synaptic transmission. So the new connections can't even work once they have sprouted. Indeed, the harder one works to use rehabilitative training to improve recovery the thicker the net becomes. It's formation is activity dependent. Therefore, we injected the enzyme farther down the spinal cord at the level of C4-5 to remove the net around the motor nerve cells that receive the newly sprouted amplifying connections from the local interneurons and serotonergic system. In turn, the motor neurons send their axons out to the muscles (we targeted motor neurons that go out to the diaphragm and upper forearm). The results were amazing with full and rapid recovery after a near lifetime of paralysis. We think this fast recovery is due to the enzyme unmasking the new connections that had already formed over time. Thus, the longer the time after injury the better was the recovery. One important caveat is that when we pushed respiratory rehab too hard in combination with the enzyme ( a strategy called acute intermittent hypoxia) then in some animals, instead of getting nicely patterned respiratory functional recovery, a debilitating chaotic activity developed. We learned that this unwanted activity occurred because the combo strategy caused too much serotonergic sprouting. So we now have to work out what the optimal strategy is to maximize the speed and amount of recovery.
                              Dr. Silver--Thank you for that detailed and complex explanation. Think I learned two important things in your explanation. First, the injection of the enzyme was at 2-3 levels (C4-5) below the level of injury at C2, and not focused on the glial scar area. Second, too much focused rehab after the injection was a hindrance to the best possible recovery. In the long run, this may help solve and reduce the time, effort, and cost issue of extensive and expensive walking 6/6/6/ rehab thought to be completely necessary to regain function. So pleased with the testing on chronic injuries.

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