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  • Renetx bio

    13-Jul-20
    ReNetX Bio Announces Key Scientific Publication Validating Preclinical Translation with Lead Molecule

    https://academic.oup.com/brain/artic...dFrom=fulltext

    Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury

    Xingxing Wang, Tianna Zhou, George D Maynard, Pramod S Terse, William B Cafferty, Jeffery D Kocsis, Stephen M Strittmatter
    Brain, Volume 143, Issue 6, June 2020, Pages 1697–1713, https://doi.org/10.1093/brain/awaa116
    Published:

    06 May 2020
    Article historyAbstract

    After CNS trauma such as spinal cord injury, the ability of surviving neural elements to sprout axons, reorganize neural networks and support recovery of function is severely restricted, contributing to chronic neurological deficits. Among limitations on neural recovery are myelin-associated inhibitors functioning as ligands for neuronal Nogo receptor 1 (NgR1). A soluble decoy (NgR1-Fc, AXER-204) blocks these ligands and provides a means to promote recovery of function in multiple preclinical rodent models of spinal cord injury. However, the safety and efficacy of this reagent in non-human primate spinal cord injury and its toxicological profile have not been described. Here, we provide evidence that chronic intrathecal and intravenous administration of NgR1-Fc to cynomolgus monkey and to rat are without evident toxicity at doses of 20 mg and greater every other day (≥2.0 mg/kg/day), and far greater than the projected human dose. Adult female African green monkeys underwent right C5/6 lateral hemisection with evidence of persistent disuse of the right forelimb during feeding and right hindlimb during locomotion. At 1 month post-injury, the animals were randomized to treatment with vehicle (n = 6) or 0.10–0.17 mg/kg/day of NgR1-Fc (n = 8) delivered via intrathecal lumbar catheter and osmotic minipump for 4 months. One animal was removed from the study because of surgical complications of the catheter, but no treatment-related adverse events were noted in either group. Animal behaviour was evaluated at 6–7 months post-injury, i.e. 1–2 months after treatment cessation. The use of the impaired forelimb during spontaneous feeding and the impaired hindlimb during locomotion were both significantly greater in the treatment group. Tissue collected at 7–12 months post-injury showed no significant differences in lesion size, fibrotic scar, gliosis or neuroinflammation between groups. Serotoninergic raphespinal fibres below the lesion showed no deficit, with equal density on the lesioned and intact side below the level of the injury in both groups. Corticospinal axons traced from biotin-dextran-amine injections in the left motor cortex were equally labelled across groups and reduced caudal to the injury. The NgR1-Fc group tissue exhibited a significant 2–3-fold increased corticospinal axon density in the cervical cord below the level of the injury relative to the vehicle group. The data show that NgR1-Fc does not have preclinical toxicological issues in healthy animals or safety concerns in spinal cord injury animals. Thus, it presents as a potential therapeutic for spinal cord injury with evidence for behavioural improvement and growth of injured pathways in non-human primate spinal cord injury.
    axon, regeneration, oligodendrocyte, Nogo receptor, spinal cord injury
    Topic:
    Issue Section:
    Original Articles


    "I'm manic as hell-
    But I'm goin' strong-
    Left my meds on the sink again-
    My head will be racing by lunchtime"

    <----Scott Weiland---->

  • #2
    I thought this was going to be a publication of Phase I results.

    Comment


    • #3
      Originally posted by Sparky831 View Post
      I thought this was going to be a publication of Phase I results.
      does anyone know approx when that will be?
      "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

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      • #4
        What are you looking to hear? Phase 1 is just safety.

        Comment


        • #5
          Originally posted by niallel View Post
          What are you looking to hear? Phase 1 is just safety.
          Maybe subjects in the higher dosage group experienced some changes?

          Comment


          • #6
            I wasn't trying to be sarcastic, although it did come across like that when I re-read, apologies for that.

            What I meant was that these interim reports that get published are usually rubbish, and say things like "Successful Safety Trial" or "Promising Improvements".

            I've not heard much about it for a while so I'll ask what the status is.

            Comment


            • #7
              Originally posted by niallel View Post
              I wasn't trying to be sarcastic, although it did come across like that when I re-read, apologies for that.

              What I meant was that these interim reports that get published are usually rubbish, and say things like "Successful Safety Trial" or "Promising Improvements".

              I've not heard much about it for a while so I'll ask what the status is.
              nice
              "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

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              • niallel
                niallel commented
                Editing a comment
                Got an out of office until 7th August, but will report back what I hear.

            • #8
              Originally posted by lunasicc42 View Post

              nice
              Who did you email?

              Comment


              • niallel
                niallel commented
                Editing a comment
                Executive Director of the Wings for Life Accelerated Translational Program who is looking after the RenetX trial.

            • #9
              Got fobbed off with not allowed to say. Pah!

              Did get given a new article on it though which I've attached.
              Attached Files

              Comment


              • #10
                I think I'm going to try and enroll again. I'm waiting on StemCyte's trial, but it's taking forever.

                Comment


                • #11
                  Any access to Trial for Canadians?
                  www.MiracleofWalk.com

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

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