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Thread: Dr. Jerry Silver: Latest chronic SCI research results featured at Cleveland

  1. #81
    Quote Originally Posted by JamesMcM View Post
    This may be a stupid question but is this "peptide" taken orally, or is it injected into the injury site on the spinal cord? Also is chase planned to be used alone or is it to be a part of the peptide?

    The peptide is delivered systemically once per day either via sub-cutaneous or intra peritoneal injection. Experiments are now underway in chronically injured animals where we are combining ch'ase and the peptide.

  2. #82
    Quote Originally Posted by jsilver View Post
    The peptide is delivered systemically once per day either via sub-cutaneous or intra peritoneal injection. Experiments are now underway in chronically injured animals where we are combining ch'ase and the peptide.
    Can you tell us what injury model you are using along with which kind of ch'ase is involved in these chronic experiments?

  3. #83
    Quote Originally Posted by GRAMMY View Post
    Can you tell us what injury model you are using along with which kind of ch'ase is involved in these chronic experiments?
    We are using a T8 severe contusive injury and then allowing the animals to age 3 months before beginning treatment. We are using regular (Sigma) ch'ase +peptide, lenti-ch'ase + peptide as well as peptide alone and lenti-ch'ase alone.

    While there is some recovery with the regular ch'ase + peptide the viral ch'ase +peptide seems to be better.

  4. #84
    Quote Originally Posted by jsilver View Post
    We are using a T8 severe contusive injury and then allowing the animals to age 3 months before beginning treatment. We are using regular (Sigma) ch'ase +peptide, lenti-ch'ase + peptide as well as peptide alone and lenti-ch'ase alone.

    While there is some recovery with the regular ch'ase + peptide the viral ch'ase +peptide seems to be better.
    Sounds great! Thanks so much.

  5. #85
    Senior Member lynnifer's Avatar
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    Large animal studies already???? That is fantastic to hear for those younger than I!
    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

  6. #86
    Dr. Silver I'm sure this is a very important question for most of us, but after a successful large animal study or if necessary a phase 1 safety is completed, do you think that your peptide could be given to sci patients under compassionate use? Many of us would be willing to take the risk , I mean a lot of us are praying we don't wake up... But when given a fair shot for recovery I know for a fact there's many people like myself that would go above and beyond to improve their quality of life. And as a high cervical injury every little function has dramatic implications. I understand that this is a difficult question to answer, but if you could give your best educated attempt that would be greatly appreciated.

  7. #87
    Quote Originally Posted by jsilver View Post
    Their model involves the production of trails that might be used to guide axons over lengthy distances. Whether this strategy will work or not could be a topic for discussion elsewhere. Our model does not need such elaborate trail making machinery. We only need to inject via a micro needle into appropriate levels of the cord. No need for invasive procedures with our technique.

    Dr. Silver, I am guessing you believe there is fault in their neuro trail theory for regeneration. I can respect that you may not want to speak negatively; but, can you elaborate a little on your concerns? It seems they too are trying to be less invasive in their application for chronics.


    There is some that believe Invivo's scaffold may become the standard of care for acute injury. You have described the peptide alone as effective in the acute injury. If asked, would you consider inclusion of the peptide with the scaffold?
    please . . .test what you already know; and give us what you have. we may not be dying, but we certainly are not living either

  8. #88
    Quote Originally Posted by JamesMcM View Post
    Dr. Silver I'm sure this is a very important question for most of us, but after a successful large animal study or if necessary a phase 1 safety is completed, do you think that your peptide could be given to sci patients under compassionate use? Many of us would be willing to take the risk , I mean a lot of us are praying we don't wake up... But when given a fair shot for recovery I know for a fact there's many people like myself that would go above and beyond to improve their quality of life. And as a high cervical injury every little function has dramatic implications. I understand that this is a difficult question to answer, but if you could give your best educated attempt that would be greatly appreciated.
    Dear JamesMcM,

    Yes, for sure this is a difficult question that I am not able to answer. I know little about the rules that govern compassionate use. But let us first demonstrate a successful strategy that
    is robust and efficacious after chronic SCI. This is the major focus of my lab.

  9. #89
    Quote Originally Posted by Nicksdad View Post
    Dr. Silver, I am guessing you believe there is fault in their neuro trail theory for regeneration. I can respect that you may not want to speak negatively; but, can you elaborate a little on your concerns? It seems they too are trying to be less invasive in their application for chronics.



    There is some that believe Invivo's scaffold may become the standard of care for acute injury. You have described the peptide alone as effective in the acute injury. If asked, would you consider inclusion of the peptide with the scaffold?
    The sequence of our peptide is published and can be purchased by anybody. It would , indeed, be interesting to learn if it can be used in a combinatorial strategy with a bioscaffold. In regards to trail building, one of the most
    perplexing phenomena that regenerating axons display is their refusal often to abandon a growth promoting surface to continue beyond the trail into the parenchyma of the gray matter in order to make functional synapses. There are techniques that have been devised to lure axons into gray matter via exogenous neurotrophins or the administration of chondroitinase at the end of the bridge to allow them to exit, but it is not clear that these additional tools are being considered. The bottom line is that trail blazing for regeneration is very complicated.

  10. #90
    Prof Silver,

    do you think Ch'ase could work better in combination with this?

    Title: Functional recovery from chronic spinal cord injury by the reactivation of endogenous microglia




    During the chronic phase of spinal cord injury (SCI), fibrotic scar tissue was formed as if it was a barrier for regeneration. We hypothesized that reactivation of resting microglia, which are the resident macrophage in spinal cord, might eliminate such a structural barrier to prevent functional recovery. First, we investigated whether p38 MAP kinase (p38) could be an activator of residential microglia obtained from mice spinal cord. The addition of dominant active type of recombinant p38 protein (DA) to the culture medium promoted the activation of cultured microglia; the increased expression of growth factors including Glial cell-line derived neurotrophic factor, the phagocytotic clearance of spinal cord debris, and rapid phosphorylation of membrane protein obtained from the cultured microglia. In addition, continuous infusion of DA protein into the mice spinal cord for 7 days increased the number of Iba1-positive microglia. These results suggested that DA protein is an activator for microglia in the spinal cord. To ascertain the effect of DA protein on the chronic phase of SCI, DA injection into spinal cord was started three months after the contusion injury, and DA was injected intrathecally once a week for 2.5 months. Immunohistochemical analysis with anti-collagen antibody showed a significant reduction of scar tissue formation by long-term DA injection. Furthermore, rota rod test and BMS score revealed that DA-injected mice showed the improvement in motor function compared to the mice injected with p38 protein which lost kinase activity. These results suggest that DA protein provides a reasonable approach for functional recovery from chronic SCI by activating endogenous microglia from outside cells.
    Society for Neuroscience Chicago 2015 Nanosymposium SCI: Therapeutic Strategies Trauma
    Support: KAKENHI 22500340 KAKENHI 24300197 the Strategic Research Foundation Grant-aided Project for Private Schools at Heisei 23rd from the Ministry of Education, Culture, Sports, Science and Technology of Japan, 2011?2015
    Authors: *M. HAMANOUE1,2, K. MORIOKA3, K. HAYAKAWA4, K. NAKAJIMA5, T. OGATA6, K. TAKAMATSU1,2; 1Dept. of Physiol., Toho University Sch. of Med., Tokyo, Japan; 2Div. of Chronic Inflammatory Diseases, Advanced Med. Res. Ctr., Toho Univ. Grad. Sch. of Med., Tokyo, Japan; 3Neurolog. Surgery, Brain and Spinal Injury Ctr. (BASIC), San Francisco, CA; 4Orthopaedic Surgery, The Univ. of Tokyo, Grad. Sch. of Med., Tokyo, Japan; 5Sci. and Engin. for Sustainable Innovation, Fac. of Sci. and Engin., Soka Univ., Tokyo, Japan; 6Rehabil. for the Movement Functions, Natl. Rehabil. Ctr. for Persons with Disabilities, Saitama, Japan
    In God we trust; all others bring data. - Edwards Deming

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