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Dr Martin Schwab - Switzerland.

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    #61
    No matter what so but we have great hope in you dear Jerry. Nice to see your comments after some time on cc. God bless you and we want just chase as soon as possible.

    Comment


      #62
      Originally posted by mamadavid View Post
      Dear Dr Silver,

      Are you convinced that further trials of Nogo are a waste of time?
      Here is the definitive answer to your question.

      Journal of Neurotrauma
      ..
      Delayed Anti-Nogo-A Antibody Application after Spinal Cord Injury Shows Progressive Loss of Responsiveness

      Roman R. Gonzenbach,1 Bjoern Zoerner,2 Lisa Schnell,2 Oliver Weinmann,2 Anis K. Mir,3 and Martin E. Schwab4
      1UniversitätsSpital Zürich, Neurologische Klinik, Zürich, Switzerland.
      2Brain Research Institute, University of Zurich, Switzerland, Zürich, Switzerland.
      3Novartis Pharma, Basel, Switzerland.
      4University and ETH Zurich, University of Zurich, Switzerland, Zürich, Switzerland.

      ABSTRACT


      Blocking the function of the myelin protein Nogo-A or its signaling pathway is a promising method to overcome an important neurite growth inhibitory factor of the adult central nervous system (CNS), and to enhance axonal regeneration and plasticity after brain or spinal cord injuries. Several studies have shown increased axonal regeneration and enhanced compensatory sprouting, along with substantially improved functional recovery after treatment with anti-Nogo-A antibodies, Nogo-receptor antagonists, or inhibition of the downstream mediator RhoA/ROCK in adult rodents. Proof-of-concept studies in spinal cord-injured macaque monkeys with anti-Nogo-A antibodies have replicated these findings; recently, clinical trials in spinal cord-injured patients have begun. However, the optimal time window for successful Nogo-A function blocking treatments has not yet been determined. We studied the effect of acute as well as 1- or 2-weeks delayed intrathecal anti-Nogo-A antibody infusions on the regeneration of corticospinal tract (CST) axons and the recovery of motor function after large but anatomically incomplete thoracic spinal cord injuries in adult rats. We found that lesioned CST fibers regenerated over several millimeters after acute or 1-week-delayed treatments, but not when the antibody treatment was started with a delay of 2 weeks. Swimming and narrow beam crossing recovered well in rats treated acutely or with a 1-week delay with anti-Nogo-A antibodies, but not in the 2-week-delayed group. These results show that the time frame for treatment of spinal cord lesions with anti-Nogo-A antibodies is restricted to less than 2 weeks in adult rodents.

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        #63
        If I have understood, what this study shows is that what we believed for years as hope of future treatment for chronic patients, apparently does not work, at least the way it was used in this study.

        Comment


          #64
          Originally posted by jsilver View Post
          Here is the definitive answer to your question.
          So not a total waste, but a waste for chronics. Bummer.

          Comment


            #65
            Another piece of the puzzle.

            Comment


              #66
              Its really very very sad for chronics. Now where we should look for cure?

              Jerry how do u see neural stem cells as potential candidate for chronic spinal injuries specially for all levels of injuries?

              Comment


                #67
                Originally posted by Jawaid View Post
                Its really very very sad for chronics. Now where we should look for cure?

                Jerry how do u see neural stem cells as potential candidate for chronic spinal injuries specially for all levels of injuries?

                Frankly, I was not surprised by this latest result from the Schwab lab and he is to be commended for publishing the negative results of his sub-chronic studies. The myelin inhibition story has become increasingly controversial since it was first introduced about 2 decades ago, with a number of good labs failing to see any evidence of axonal regeneration as well as behavioral recovery even at acute stages, let alone chronic. There is still some evidence that manipulation of Nogo or its receptors may elicit some level of functional plasticity via sprouting at least at acute stages after SCI. Recently, the Strittmatter lab has reported that a so-called Nogo receptor decoy protein can restore some level of function when the protein is delivered via intrathecal catheter 3 months after contusive injury in mice. Again, such claims need to be replicated by other labs and in larger mammals, so we need to temper enthusiasm. As far as stem cells go, again, I have been quite passionate in my beliefs, based firmly on the scientific evidence, that “stem cells” surely will have their place at acute stages after injury. A variety of stem cells (and perhaps some more than others) have powerful anti-inflammatory and/or trophic effects. I have seen this with my own eyes, in my own lab and we have published our results. Thus, many types of stem cells can be neuroprotective for a time after injury and may even foster a measure of beneficial sprouting in the vicinity of the lesion. The question remains: how much time can elapse after injury before stem cell therapy loses its effectiveness once the inflammatory cascade winds down and the wound becomes socked in by scar tissue? Thus far, there is no compelling evidence in the literature that stem cells have robust therapeutic effects after SCI when administered at chronic stages (ie., beyond about 6 weeks after injury). Specific types of stem cells may be able to migrate away from the injury site and re-myelinate gaps in otherwise healthy axons even at sub-chronic stages after SCI. In this regard, the best work I have seen is that from Aileen Anderson and Brian Cummings and you all know about StemCells Inc. Let’s keep our fingers crossed on that one. I still have a profound optimism that if the right mixture of labs that have shown the very best results with their individual approaches (a sort of scientific dream team) could come together in a collaborative effort, we will surely be able to devise a strategy that can foster a good measure of functional improvement at long chronic stages. Indeed, we have seen (and I reported preliminary evidence at W2W 2011) a remarkable return of diaphragm function (the diaphragm had been paralyzed by a C2 hemisection one full year earlier!) within one week following a single injection of chondrotinase applied near the phrenic motor pool. Since this can happen (and we have yet to combine appropriate rehab and/or FES or additional molecular therapies) then surely far more is possible. For those with complete injuries, there are bridge building strategies that are beginning to look incredibly promising so, again, with continuing, scientifically rigorous success, there is hope.

                Comment


                  #68
                  Thank u so much dear Jerry for always replying.

                  We all CC friends have been waiting very very anxiousely for your meeting with acorda in April. We will surely keep an eye over Stem cells Inc trial.

                  I m sure Jerry you will do ur best to bring chase into clinical trial as soon as possible on the behalf of we all.Your meeting is being waited here.

                  Comment


                    #69
                    Thanks for posting Jerry

                    Comment


                      #70
                      Jerry are neural stem cells same which StemCell Inc is using and Neuralstem will be using for phase one with chronic injuries soon as they have applied with FDA?

                      Also www.stemedics.com have shown good results with animals with their neural cells. So are these same neural stem cells or some difference?

                      Is it true that through IV or spinal fluid injection stem cells dont reach injury site in chronic injuries than direct injections at injury site in and around? What is the best method to go with?
                      Are lumbar injuries hard to treat than cervical and thoracic injuries or may be easier?

                      Comment


                        #71
                        Originally posted by Jawaid View Post
                        Jerry are neural stem cells same which StemCell Inc is using and Neuralstem will be using for phase one with chronic injuries soon as they have applied with FDA?

                        Also www.stemedics.com have shown good results with animals with their neural cells. So are these same neural stem cells or some difference?

                        Is it true that through IV or spinal fluid injection stem cells dont reach injury site in chronic injuries than direct injections at injury site in and around? What is the best method to go with?
                        Are lumbar injuries hard to treat than cervical and thoracic injuries or may be easier?
                        Sorry it is www.stemedica.com

                        Comment


                          #72
                          https://docs.google.com/viewer?a=v&q...4XeYLbB4P7Zr3Q

                          Comment


                            #73
                            Nice layout of the phases of trials, fti.
                            Courage doesn't always roar. Sometimes courage is the quiet voice at the end of the day saying, "I will try again tomorrow."

                            Disclaimer: Answers, suggestions, and/or comments do not constitute medical advice expressed or implied and are based solely on my experiences as a SCI patient. Please consult your attending physician for medical advise and treatment. In the event of a medical emergency please call 911.

                            Comment


                              #74



                              Dear Patrick,

                              I am contacting you with regard to your interest in the Nogo-A antibody therapy in spinal cord injured patients.

                              We performed a phase I safety study which was completed in 2011. You will find more information about this study at: https://clinicaltrials.gov/ct2/show/NCT00406016

                              We plan to perform a multicenter European clinical phase II study and are currently applying for funding resources. If we receive the resources the study might start at the end of 2015. In the planned study only fresh spinal cord injuries (1-2 months after injury) will be addressed, because we assume that the treatment is most efficient in these patients.

                              Let me know in case you should have any additional questions.

                              Kind regards,
                              Christina Sina



                              -----
                              Dr. Christina Sina
                              Scientific Coordinator Schwab Group

                              Brain Research Institute
                              University of Zurich
                              Winterthurerstrasse 190
                              CH-8057 Zurich
                              Switzerland

                              Email: sina@hifo.uzh.ch
                              Phone: +41-44-63-53262

                              Comment


                                #75
                                Was there any functional improvement in the phase 1 study?

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