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    Originally posted by KIM View Post
    Can we know their answer?
    They tell me that they are not ready. Wise.

    Comment


      I have started thread with this topic on Exercise Forum:
      /forum/showthread.php?t=190450
      www.MiracleofWalk.com

      Miracles are not contrary to nature, but only contrary
      to what we know about nature
      Saint Augustine

      Comment


        Originally posted by comad View Post
        Maybe I wasn't clear enough.
        I am asking about walking program details - Not about cells or surgery.
        I was reading all posts from Dr. Wise and his observation how they doing this walking (pulling knees to lock with ropes etc.) and that's good resource.
        There are some fine tweaks and details related to individual needs where PT with experience in this type of walking can help a lot answering to specific member questions. I have suggested to Dr. Wise to hook-up someone from Kunming with more time and specific knowledge to Exercise & Recovery forum.
        I know that language is barrier but simple q&a can be easily google-translated.
        Comad,

        Please understand that this is work of Dr. Hui Zhu and her colleagues. She recently retired (required due to age) from the Army General Hospital in Kunming and is in the process of moving to a private hospital in Kunming. The details of the training procedure that you are asking have not been published in English. I am not sure that they have been published in Chinese either. Dr. Zhu developed and applied these methods to thousands of patients. Yes, she has videos of individual patients but this is not the same as instructional materials.

        At ChinaSCINet, we have been doing our best to help them gather the evidence that intensive walking helps restore function and to introduce their method to other doctors. Over the past several years, I have brought many doctors and people from the community to observe. One member of CareCure will be spending time there to help translate and to make it easier for families to visit. We have even brought doctors from Kunming to Rutgers to speak in our Open Houses.

        At the present, there is nobody in Kunming with sufficient knowledge of English to answer questions of the type that you want to ask. I also want to suggest that this is asking a lot for any group to do and they will be criticized for doing so because their walking procedure is considered experimental. So, please be patient. I think that as soon as Dr. Zhu and her colleagues are settled in the new hospital and restarts her program, they will welcome visitors and perhaps people can help translate and transfer technology.

        Wise.

        Comment


          Originally posted by Johnnie Walker View Post
          But Acorda does not have the patent in China too? so you can do it without Acorda?
          Johnnie,

          This is not a matter of having a patent in China. Nobody has a GMP (good manufacturing practice) source of chondroitinase that can be put into patients. Acorda (or whoever) must do a lot of work and invest a lot of money into making such a source of chondroitinase. They are not ready to do this. To my knowledge, nobody else is investing in manufacturing chondroitinase for clinical trial.

          It will be a multimillion investment and it will take years to establish such a GMP source. Chondroitinase is an enzyme made by Proteus vulgaris. To manufacture the drug, many strains of bacteria must be tested, characterized, and then used to manufacture chondroitinase that must be in turn tested in vitro and in vivo. After the best bacteria and manufacturing conditions are established, a master cell bank must be established that would allow the work to be reproduced. The drug must be formulated and each formulation must be tested and optimized.

          There are also many obstacles to approval for regulatory agencies to approve the clinical trials. First, proteus vulgaris is a common bacterium that participates in bladder infections. It is likely that many people with spinal cord injury have antibodies against chondroitinase. The FDA may well require this information before they will approve a clinical trial. Second, chondroitinase is an enzyme that is quite heat-sensitive and does not last long after injection into the spinal cord. FDA will require enzyme activity, stability, and degradation information. If it is injected into the spinal cord, they will want to know how it is degraded, how long it is active, and whether or not it causes any toxicity.

          So, it is not a slam-dunk and it will take time and money to get a source of chondroitinase that can be injected into the spinal cord.

          Wise.

          Comment


            Originally posted by Wise Young View Post
            Johnnie,

            This is not a matter of having a patent in China. Nobody has a GMP (good manufacturing practice) source of chondroitinase that can be put into patients. Acorda (or whoever) must do a lot of work and invest a lot of money into making such a source of chondroitinase. They are not ready to do this. To my knowledge, nobody else is investing in manufacturing chondroitinase for clinical trial.

            It will be a multimillion investment and it will take years to establish such a GMP source. Chondroitinase is an enzyme made by Proteus vulgaris. To manufacture the drug, many strains of bacteria must be tested, characterized, and then used to manufacture chondroitinase that must be in turn tested in vitro and in vivo. After the best bacteria and manufacturing conditions are established, a master cell bank must be established that would allow the work to be reproduced. The drug must be formulated and each formulation must be tested and optimized.

            There are also many obstacles to approval for regulatory agencies to approve the clinical trials. First, proteus vulgaris is a common bacterium that participates in bladder infections. It is likely that many people with spinal cord injury have antibodies against chondroitinase. The FDA may well require this information before they will approve a clinical trial. Second, chondroitinase is an enzyme that is quite heat-sensitive and does not last long after injection into the spinal cord. FDA will require enzyme activity, stability, and degradation information. If it is injected into the spinal cord, they will want to know how it is degraded, how long it is active, and whether or not it causes any toxicity.

            So, it is not a slam-dunk and it will take time and money to get a source of chondroitinase that can be injected into the spinal cord.

            Wise.
            Seikagaku Corporation took the research reagent off the market because they are currently running clinical trials in Japan with Chondroitinase ABC under a generic name called "Condoliase" for disc hernia. They finished Phase 1 and 2 but have now requested a Phase 3 to begin. A Phase 2 has also been requested of the FDA here in the USA but the indication is strictly for disc hernia. Seikagaku Corporation won't run a clinical trial for sci as long as the disc hernia human trial is running because of the expenses. They would need financial help to run a CT for sci (in Japan anyway).

            http://clinicaltrials.gov/ct2/show/NCT00634946 SI-6603 is generic named "Condoliase" (Chondroitinase ABC)

            http://clinicaltrials.gov/ct2/show/NCT01282606

            Here's the structural formulation for "Condoliase": http://www.ama-assn.org/resources/do...condoliase.pdf
            Last edited by GRAMMY; 16 Jun 2012, 2:55 PM.
            http://spinalcordresearchandadvocacy.wordpress.com/

            Comment


              Originally posted by GRAMMY View Post
              Seikagaku Corporation took the research reagent off the market because they are currently running clinical trials in Japan with Chondroitinase ABC under a generic name called "Condoliase" for disc hernia. They finished Phase 1 and 2 but have now requested a Phase 3 to begin. A Phase 2 has also been requested of the FDA here in the USA but the indication is strictly for disc hernia. Seikagaku Corporation won't run a clinical trial for sci as long as the disc hernia human trial is running because of the expenses. They would need financial help to run a CT for sci (in Japan anyway).

              http://clinicaltrials.gov/ct2/show/NCT00634946 SI-6603 is generic named "Condoliase" (Chondroitinase ABC)

              http://clinicaltrials.gov/ct2/show/NCT01282606

              Here's the structural formulation for "Condoliase": http://www.ama-assn.org/resources/do...condoliase.pdf
              Grammy,

              Thank you very much for posting the information. As you know, the Seikagaku trial was completed and closed last year (2011). The trial tested their chondroitinase (SI-6603, condoliase), formulated and directed at the Japanese disc herniation market http://www.seikagaku.co.jp/english/i...u2012_2q_e.pdf.

              I use to work with Seikagaku, when they were interested in pursuing spinal cord injury. We trained a team from the company to do animal studies of the drug. The company decided not to pursue spinal cord injury as an indication and let go of the spinal cord injury team from the company.

              To my knowledge, that Seikagaku version of chondroitinase has not since been developed or tested for spinal cord injury within the company. Seikagaku recently licensed chondroitinase to Kaken Pharma, i.e. http://www.thepharmaletter.com/file/...-to-kaken.html.

              To obtain chondroitinase for spinal cord injury trials, we must have a GMP source of the drug, tested for safety and efficacy in administration to the spinal cord. To my knowledge, such a source is not available at the present.

              Wise.

              Comment


                If that version of the chondroitinase abc was SAFE AND GOOD for disk hernia clinical trial , why that version is not good and safe enough for chronic spinal cord injury trial now?I am assuming in that clinical trial (phase 1 and 2 , etc. ), the safety of the drug has been validated, proven and established .
                Last edited by kz; 16 Jun 2012, 5:18 PM.

                Comment


                  Originally posted by kz View Post
                  If that version of the chondroitinase abc was SAFE AND GOOD for disk hernia clinical trial , why that version is not good and safe enough for chronic spinal cord injury trial now?I am assuming in that clinical trial (phase 1 and 2 , etc. ), the safety of the drug has been validated, proven and established .
                  kz,

                  Spinal cord is different from a herniated disc. A disc is a piece of connective tissue and it doesn't matter if some cells die in the disc after the injection. Injecting into the spinal cord injury completely different. You don't want to kill any cells. Of course, some investigators have used the Seikagaku chondroitinase to treat rodent spinal cords but you need formal safety pathological analyses of the spinal cord under GLP (Good Laboratory Practice) conditions. I don't know (and don't think) that Seikagaku has "validated, proven, and established" the safety of the drug for administration into the spinal cord of rodents and a non-rodent species, as required by the FDA.

                  Wise.

                  Comment


                    Dear Dr. Young ,
                    Thanks so much indeed .

                    Comment


                      Originally posted by kz View Post
                      Dear Dr. Young ,
                      Thanks so much indeed .
                      You are very welcome.

                      I don't mean to be discouraging but I want to emphasize that it takes much work and time to prepare any treatment for trial. That is one of the reasons why we are designating treatments of interest as early as we can so the necessary work be done to obtain essential data to get approval of the therapy for trial. it took us years to get umbilical cord blood cells and lithium ready for trial. We will need to do the same for the therapies that we want to take to trial in 2014. Please note that there is currently no GMP source of Cethrin or Muse cells either. Can you imagine what would happen if a tumor developed from the cells or chondroitinase made somebody worse? It would kill not only the therapy and also the careers of the investigators.

                      Perhaps this is a good time to defuse assumptions that some people seem to be making. First, people should stop assuming that all we have to do is to inject some cells and drugs into the spinal cord. The therapies must meet the highest standards of safety and reliability in order to pass muster with the FDA and other regulatory agencies. Second, the therapies are not "mine". The therapies we choose to test are what my colleagues and I believe are the best promising and feasible therapies available for chronic spinal cord injury. Feasible means that the therapies are available, have undergone the necessary safety tests, and have a reasonable chance of showing efficacy. Third, we are still discussing the therapies for 2014. The only decision that has been made is that we are going ahead with the UCBMC and lithium phase 3. Fourth, we don't yet have funding for the planned phase 3 trials. People assume that the trials are going ahead with no funding. All our decisions are constrained by the availability of funds. We may have to delay these trials if we don't raise the funds.

                      Wise.
                      Last edited by Wise Young; 17 Jun 2012, 12:23 PM.

                      Comment


                        Wise how much is needed to do phase 3?

                        Comment


                          wise, we see that differet foundations are getting million of dollars from differnt methods. You seem to be the most efficeint in bringing therapies to trials. Why is it that monies don't come your way? Is there amything that we can do, other than personal contributions, to help? Also, can we get to real dates on phase 3 trials for china and phase 3 trials for the USA? Is there a real chance that UCBC ANd LITHIUM WILL WORK FOR MANY OF US TO IMPROVE FUNCTION, LIKE WALKING AND BOWEL ANd BLADDER, i KNOW YOU HAVe ANSwERED SOMe OF THESE QUESTIONS BEFORE, but we need to know the truth at this time. In other words talking about 2014 just to start trials with cethrin means we are years away from any real treatment that will benefit many of us. Please be specific if you decide to answer these questions.

                          anthony

                          Comment


                            Originally posted by Wise Young View Post
                            Everybody,

                            People can ask questions and don't have to donate money to ask questions. What people don't have the right to do here on CareCure is to question somebody's honesty, integrity, motivation, intelligence, or work ethics when asking questions. That just leads to anger, erodes friendships, and causes miscommunication.

                            Wise.
                            ----------------------

                            Paolo,

                            Please be patient. I have been writing an answer to your question and it is taking more time than I had thought. I should have posted that I will be answering part of your question. By the way, please do not expect me to present detailed data about our study and you simply will have to wait until we have it accepted for publication before I present such data.

                            Wise.

                            Magnetic resonance diffusion tensor imaging (MR-DTI)

                            Magnetic resonance diffusion tensor imaging (MR-DTI) is a method of analyzing magnetic resonance data so that it shows water diffusion. As you know, standard magnetic resonance detects water (H2O). Water is the most abundant molecule in biological tissues and excitation of H2O by pulses of electromagnetic energy in a strong magnetic field will perturb the molecule so that it emits energy back in a specific frequency. Movement of water produces changes of magnetic resonance in sequential snapshots of the tissue. Normally, in non-oriented tissues, water diffuses in all directions. However, in oriented tissues, the diffusion will be more restricted in some directions than others. This property is called anisotrophy.

                            White matter is the most oriented tissues in the central nervous system, containing bundles of fibers running longitudinally for long distances. Also called diffusion MRI (dMRI), MR-DTI has been used for mapping diffusion in brain tissues since the early 1980's. During the last 25 years, it has been applied to many neurological conditions and has served as the basis of the Human Brain Connectome project, which is building maps of anatomical and functional connections of the human brain. Many studies have now been published on MR-DTI of spinal white matter. For example, a search "diffusion tensor imaging" and "spinal cord" on Google Scholar yielded over 150 published articles on the subject.

                            Software is now available for a user to select an area of interest (i.e. white matter above the injury site or below the injury site) and the program will find contiguous tissues that show the same directional diffusion characteristics. In other words, the software will show bundles of oriented fibers that are contiguous with each other. By doing so, we can see the white matter above the injury site and below the injury site. If any white matter tracts were to regrow across the injury site, we should be able to see them cross the injury site. So, we used MR-DTI in our trial to identify the injection sites (at the white matter wave fronts rostral and caudal to the injury site) and to detect white matter growth across in the injury site. The degree and volume anisotrophy can be quantified to assess white matter change.

                            Mulcahey, et al. [1] at Shriner’s hospital recently examined the DTI images of children with spinal cord injury. They found good-to-strong reliability on repeated scans and moderate-to-good concurrent validity with clinical (ASIA) classifications of the injury. They concluded that DTI is a better predictor of clinical findings (i.e. AIS A, B, C, D, E) than conventional MRI. Freund, et al. [2] imaged nine adult volunteers with cervical spinal cord injury and found significant differences of corticospinal tract of SCI subjects compared to controls, including ability to predict paralysis of different parts of the body. Bosma & Stroman [3] reviewed studies using DTI to visualize spinal cords in patients with amyotrophic lateral sclerosis, myelitis, and spinal cord tumors. Smith, et al. [4] at Kennedy Krieger in Baltimore reported that DTI images can reliably discriminate sensory and motor tracts. Ellington, et al. [5] compared four subjects with spinal cord injury with 4 normal subjects. They found a general decrease in both longitudinal and transverse diffusivity in the former.

                            Many investigators have used DTI to investigate animal models of spinal cord injury. Tu, et al. [6] at Washington University in St. Louis used DTI to quantify spared white matter in mice after contusion injuries. Sundberg, et al. [7] used DTI to assess rats at various times up to 56 days after contusion injuries. White matter in regions up to a centimeter from the injury site showed significant changes that were not seen on conventional MRI. Histological evidence confirmed significant decrease in myelin and oligodendrocyte presence in these areas of the spinal cord, suggesting that DTI images are sensitive reflection of not only the volume but also the quality of white matter. Kim, et al. [8, 9] at Washington University showed that DTI can predict long-term locomotor recovery in mice after graded contusion injuries. Herrara, et al. [10] pointed out that while DTI can detect demyelination, axonal damage and longitudinal diffusivity (lambda) did not always correlate. Ellingson, et al. [11] found that both transverse and longitudinal diffusivity (tADC and lADC), as well as mean diffusivity (MD) and fractional anisotrophy (FA), changed over time in rodents after injury.

                            Nobody has looked at human spinal cords before and after cell transplants, or changes in white matter associated with transplants. Therefore, we planned such a study in Hong Kong. It was a very difficult study because the presence of metallic implants around the injury site distorted the images and introduced artifacts. Most patients have such metallic implants. Also, we had to work out many issues, including the parameters that would be used for imaging the white matter. We hypothesized that subjects with “complete” ASIA A spinal cord injuries would not have any white matter crossing the injury site, that injections of small amounts of cells (i.e. 4 and 8 ┬Áliters) would not change the white matter in the spinal cord, and that restoration of function would be associated with appearance of white matter bundles crossing the injury site. So, we did a study of MR-DTI images of 8 subjects with chronic SCI before and at 6 weeks, 6 months, 12 months (and 18 months) after transplantation umbilical cord blood mononuclear cells (four injections of 4 or 8 ┬Áliters) in the spinal cord above and below and injury site. These are compared with 8 normal control subjects.

                            This will be the subject of the study that we will soon submit for publication.

                            References Cited

                            1. Mulcahey MJ, Samdani A, Gaughan J, Barakat N, Faro S, Betz RR, et al. Diffusion tensor imaging in pediatric spinal cord injury: preliminary examination of reliability and clinical correlation. Spine (Phila Pa 1976). 2012;37(13):E797-803.
                            2. Freund P, Wheeler-Kingshott CA, Nagy Z, Gorgoraptis N, Weiskopf N, Friston K, et al. Axonal integrity predicts cortical reorganisation following cervical injury. J Neurol Neurosurg Psychiatry. 2012;83(6):629-37. PMCID: 3348614.
                            3. Bosma R, Stroman PW. Diffusion tensor imaging in the human spinal cord: development, limitations, and clinical applications. Crit Rev Biomed Eng. 2012;40(1):1-20.
                            4. Smith SA, Jones CK, Gifford A, Belegu V, Chodkowski B, Farrell JA, et al. Reproducibility of tract-specific magnetization transfer and diffusion tensor imaging in the cervical spinal cord at 3 tesla. NMR Biomed. 2010;23(2):207-17. PMCID: 2830283.
                            5. Ellingson BM, Ulmer JL, Schmit BD. Morphology and morphometry of human chronic spinal cord injury using diffusion tensor imaging and fuzzy logic. Ann Biomed Eng. 2008;36(2):224-36.
                            6. Tu TW, Kim JH, Wang J, Song SK. Full tensor diffusion imaging is not required to assess the white-matter integrity in mouse contusion spinal cord injury. J Neurotrauma. 2010;27(1):253-62. PMCID: 2824236.
                            7. Sundberg LM, Herrera JJ, Narayana PA. In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury. J Neurotrauma. 2010;27(10):1753-67. PMCID: 2992395.
                            8. Kim JH, Loy DN, Wang Q, Budde MD, Schmidt RE, Trinkaus K, et al. Diffusion tensor imaging at 3 hours after traumatic spinal cord injury predicts long-term locomotor recovery. J Neurotrauma. 2010;27(3):587-98. PMCID: 2867549.
                            9. Kim JH, Tu TW, Bayly PV, Song SK. Impact speed does not determine severity of spinal cord injury in mice with fixed impact displacement. J Neurotrauma. 2009;26(8):1395-404. PMCID: 2850293.
                            10. Herrera JJ, Chacko T, Narayana PA. Histological correlation of diffusion tensor imaging metrics in experimental spinal cord injury. J Neurosci Res. 2008;86(2):443-7.
                            11. Ellingson BM, Kurpad SN, Schmit BD. Ex vivo diffusion tensor imaging and quantitative tractography of the rat spinal cord during long-term recovery from moderate spinal contusion. J Magn Reson Imaging. 2008;28(5):1068-79.
                            Wise,

                            thanks for this long explaination. It actually confirmed what I knew about DTI and I learned some more.
                            If I interpret correctly the following:
                            Histological evidence confirmed significant decrease in myelin and oligodendrocyte presence in these areas of the spinal cord, suggesting that DTI images are sensitive reflection of not only the volume but also the quality of white matter. Kim, et al. [8, 9] at Washington University showed that DTI can predict long-term locomotor recovery in mice after graded contusion injuries. Herrara, et al. [10] pointed out that while DTI can detect demyelination, axonal damage and longitudinal diffusivity (lambda) did not always correlate.

                            it means that you can't decetc AXONS growing accros the injury site using a DTI as you seem to suggest in your presentation.
                            The change a DTI can show might be due just to remyelination of intact axons.

                            In any case I look forward with much interest to the publication with the DTIs.

                            Paolo
                            Last edited by paolocipolla; 17 Jun 2012, 9:13 PM.
                            In God we trust; all others bring data. - Edwards Deming

                            Comment


                              Few thousands regular viewers of this thread and few thousands regular contributors to "just a dollar please" will not make a difference.
                              We need to hire professionals to raise serious money!
                              Thinking outside of box people...
                              Something as http://www.kickstarter.com
                              or
                              Nike or Adidas sponsorship (Impossible is nothing or Just do it fits perfectly : )
                              or
                              going out to main stream media with truth and appeal for help
                              or
                              ask Paolo how to proceed

                              whatever is needed ... better than stall in this flight in this crucial moment,
                              just need a team to prepare
                              www.MiracleofWalk.com

                              Miracles are not contrary to nature, but only contrary
                              to what we know about nature
                              Saint Augustine

                              Comment


                                Originally posted by paolocipolla View Post
                                Wise,

                                thanks for this long explaination. It actually confirmed what I knew about DTI and I learned some more.
                                If I interpret correctly the following:
                                Histological evidence confirmed significant decrease in myelin and oligodendrocyte presence in these areas of the spinal cord, suggesting that DTI images are sensitive reflection of not only the volume but also the quality of white matter. Kim, et al. [8, 9] at Washington University showed that DTI can predict long-term locomotor recovery in mice after graded contusion injuries. Herrara, et al. [10] pointed out that while DTI can detect demyelination, axonal damage and longitudinal diffusivity (lambda) did not always correlate.

                                it means that you can't decetc AXONS growing accros the injury site using a DTI as you seem to suggest in your presentation.
                                The change a DTI can show might be due just to remyelination of intact axons.

                                In any case I look forward with much interest to the publication with the DTIs.

                                Paolo
                                If there were no anisotropy at the injury site before treatment, i.e. a gap, and then significant bundles of anisotropic white matter appears after the treatment, going long distances across the injury site and beyond, that would be a pretty strong argument for regeneration, don't you think?

                                Wise.

                                Comment

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