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  • Researchers repair acute spinal cord injury in monkeys

    Posted over on https://www.u2fp.org/

    Spinal cord injuries are among the most severe and difficult-to-treat medical conditions, usually resulting in permanent disability including loss of muscle function, sensation and autonomic functions. Medical research is now on the cusp of treating severe spinal cord injuries by inducing the repair of spinal nerves, and scientists have made strides in recent years with rodents and primates.

    Using chitosan loaded with neurotrophin-3 (NT3), a collaborative of Chinese medical researchers now reports the successful treatment and subsequent functional recovery of rhesus monkeys with induced acute spinal cord injuries. Though previous studies of the same treatment in rodents showed promise, these are the first results in primates, which the researchers say strongly implies its medical relevance for humans. They have published their results in The Proceedings of the National Academy of Sciences.

    Chitosan is a polysaccharide derived from the chitinous shells of shrimp and other crustaceans. It has medical applications in the reduction of bleeding and as an antibacterial agent. It is also used as a drug delivery vehicle. NT3 is a neurotrophic factor that encourages the growth and differentiation of new neurons and synapses.

    Spinal cord injury treatment and recovery is inhibited by a number of factors. Neurons in the central nervous system (CNS) do not easily regenerate in the best of conditions, and are further inhibited after injury by inflammatory cytokines and other factors.

    Previous efforts at treatment have aimed at making the post-injury CNS environment less hostile to nerve regeneration, and although researchers made some headway with rodents, these results do not translate well to humans. The researchers wanted to translate previous results from rodent studies to the treatment of non-human primates. For ethical reasons regarding the overuse of primates in medical research, they eliminated trials of several less successful variants of the chitosan-NT3 treatment and focused only on the most successful method.

    In the new study, the researchers inserted the chitosan-NT3 compound into one-centimeter gaps in hemisectioned (partially severed) thoracic spinal cords of adult rhesus monkeys. Chitosan serves as a matrix scaffold that contains and gradually releases NT3 to the injury site over a relatively long period. In the rodent studies, the NT3-chitosan scaffold inhibited inflammatory cells and attracted endogenous neural stem cells to proliferate, differentiate and eventually form neuronal networks to transmit neural signals to and from the brain.

    Using a non-invasive combination of outcome measures including fMRI, magnetic diffusion tensor imaging, and kinematics walking analyses, the researchers confirmed similar results in the rhesus monkeys. They were also able to confirm that monkeys with smaller post-treatment spinal lesions had better walking behavior. This is likely due to the anti-inflammatory action of chitosan-NT3.

    The authors write, "This study using nonhuman primates represents a substantial advancement in translating our initial study using rodents to human therapy." While the study was focused on the treatment of acute injury, they believe it will also prove applicable in treatment of chronic spinal injury.

    Explore further: Scientists discover new way to help nerve regeneration in spinal cord injury

    More information: NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury. PNAS. DOI: 10.1073/pnas.1804735115

    Abstract
    Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.


    https://medicalxpress.com/news/2018-...y-monkeys.html
    "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
    Ooo this looks cool. Did they insert the material by opening them up or just injecting it?

    Comment


    • #3
      This is a big deal for all of us!

      Comment


      • #4
        Originally posted by Jade2 View Post
        Ooo this looks cool. Did they insert the material by opening them up or just injecting it?
        Injected into the gap made by the hemisectioned surgery of the cord.
        http://spinalcordresearchandadvocacy.wordpress.com/

        Comment


        • #5
          Originally posted by GRAMMY View Post
          Injected into the gap made by the hemisectioned surgery of the cord.
          ah cheers Grammy! Hopefully this technique will prove useful for everyone at some point!

          Comment


          • #6
            Need more chronic studies!

            Comment


            • #7
              Originally posted by Sparky831 View Post
              Need more chronic studies!
              BEIJING, May 31 (Xinhua) -- Chinese researchers announced that a new type of bioactive material may help treat spinal injuries.
              Spinal cord injury (SCI) is a severe medical condition often leading to permanent loss of sensory, motor, and autonomic functions, currently with no cure, said Li Xiaoguang, professor of Beihang University and Capital Medical University. After research lasting over 20 years, Li has developed a type of bioactive and biodegradable material, NT3-chitosan. In rhesus monkeys, the material elicited robust de novo neural regeneration, sensory and motor functional recovery, said Li. The method is likely translatable to human SCI repair, he said.

              Author Information

              • [*=left]Jia-Sheng Raoa,b,c,1,
                [*=left]Can Zhaob,a,c,1,
                [*=left]Aifeng Zhangd,1,
                [*=left]Hongmei Duane,1,
                [*=left]Peng Haoe,1,
                [*=left]Rui-Han Weia,1,
                [*=left]Junkui Shange,1,
                [*=left]Wen Zhaoe,
                [*=left]Zuxiang Liuf,g,h,
                [*=left]Juehua Yui,
                [*=left]Kevin S. Fanj,
                [*=left]Zhaolong Tiank,
                [*=left]Qihua Hel,
                [*=left]Wei Songm,
                [*=left]Zhaoyang Yange,b,2,
                [*=left]Yi Eve Suni,n,2, and
                [*=left]Xiaoguang Lie,b,a,2

              • aBeijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, 100083 Beijing, China;
              • bBeijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 100083 Beijing, China;
              • cBeijing Advanced Innovation Center for Biomedical Engineering, Beihang University, 100083 Beijing, China;
              • dBeijing Friendship Hospital, Capital Medical University, 100068 Beijing, China;
              • eDepartment of Neurobiology, School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, China;
              • fState Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China;
              • gInnovation Center of Excellence on Brain Science, Chinese Academy of Sciences, 100101 Beijing, China;
              • hDepartment of Biology, College of Life Sciences, University of Chinese Academy of Sciences, 100049 Beijing, China;
              • iTranslational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China;
              • jDepartment of Computer Engineering, University of California, Santa Barbara, CA 93106;
              • kDepartment of Anesthesiology, Xuanwu Hospital Capital Medical University, 100053 Beijing, China;
              • lCentre of Medical and Health Analysis, Peking University Health Science Center, 100191 Beijing, China;
              • m Rehabilitation Engineering Research Institute, China Rehabilitation Research Center, 100068 Beijing, China;
              • 2To whom correspondence may be addressed. Email: wack_lily@163.com, yi.eve.sun@gmail.com, or lxgchina@sina.com.




              http://spinalcordresearchandadvocacy.wordpress.com/

              Comment


              • #8
                Originally posted by GRAMMY View Post
                BEIJING, May 31 (Xinhua) -- Chinese researchers announced that a new type of bioactive material may help treat spinal injuries.
                Spinal cord injury (SCI) is a severe medical condition often leading to permanent loss of sensory, motor, and autonomic functions, currently with no cure, said Li Xiaoguang, professor of Beihang University and Capital Medical University. After research lasting over 20 years, Li has developed a type of bioactive and biodegradable material, NT3-chitosan. In rhesus monkeys, the material elicited robust de novo neural regeneration, sensory and motor functional recovery, said Li. The method is likely translatable to human SCI repair, he said.

                Author Information

                • [*=left]Jia-Sheng Raoa,b,c,1,
                  [*=left]Can Zhaob,a,c,1,
                  [*=left]Aifeng Zhangd,1,
                  [*=left]Hongmei Duane,1,
                  [*=left]Peng Haoe,1,
                  [*=left]Rui-Han Weia,1,
                  [*=left]Junkui Shange,1,
                  [*=left]Wen Zhaoe,
                  [*=left]Zuxiang Liuf,g,h,
                  [*=left]Juehua Yui,
                  [*=left]Kevin S. Fanj,
                  [*=left]Zhaolong Tiank,
                  [*=left]Qihua Hel,
                  [*=left]Wei Songm,
                  [*=left]Zhaoyang Yange,b,2,
                  [*=left]Yi Eve Suni,n,2, and
                  [*=left]Xiaoguang Lie,b,a,2

                • aBeijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, 100083 Beijing, China;
                • bBeijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 100083 Beijing, China;
                • cBeijing Advanced Innovation Center for Biomedical Engineering, Beihang University, 100083 Beijing, China;
                • dBeijing Friendship Hospital, Capital Medical University, 100068 Beijing, China;
                • eDepartment of Neurobiology, School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, China;
                • fState Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China;
                • gInnovation Center of Excellence on Brain Science, Chinese Academy of Sciences, 100101 Beijing, China;
                • hDepartment of Biology, College of Life Sciences, University of Chinese Academy of Sciences, 100049 Beijing, China;
                • iTranslational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China;
                • jDepartment of Computer Engineering, University of California, Santa Barbara, CA 93106;
                • kDepartment of Anesthesiology, Xuanwu Hospital Capital Medical University, 100053 Beijing, China;
                • lCentre of Medical and Health Analysis, Peking University Health Science Center, 100191 Beijing, China;
                • m Rehabilitation Engineering Research Institute, China Rehabilitation Research Center, 100068 Beijing, China;
                • 2To whom correspondence may be addressed. Email: wack_lily@163.com, yi.eve.sun@gmail.com, or lxgchina@sina.com.




                Thank you GRAMMY

                Comment


                • #9
                  This is great. Now all they have to do is turn us into monkeys.
                  Wish I didn't know now what I didn't know then.
                  Bob Seger

                  Comment


                  • #10
                    a monkey with an acute injury
                    "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
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                    Comment


                    • #11
                      I know you're not terribly interested, but if you're paying attention, you see there's a reason the lab would go to all the trouble and high expense to take their injury model from rat to the primate model (closer to humans) that was reported above. These are the steps taken by a lab intent on bringing a therapy forward for a spinal cord injury trial and eventually to market if found worthy.

                      The authors write, "This study using nonhuman primates represents a substantial advancement in translating our initial study using rodents to human therapy." While the study was focused on the treatment of acute injury, they believe it will also prove applicable in treatment of chronic spinal injury.

                      Here is the rat model results listed below in October 2015. Take a moment to read the full publication linked below.

                      Full Publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629318/


                      SIGNIFICANCE


                      Spinal cord injury (SCI) is a debilitating medical condition with no cure at present time. In this study we have discovered that a biodegradable material, chitosan, when loaded with, Neurotrophin-3 (NT3), allowed for slow release of this neural trophic factor, providing an optimal microenvironment for regeneration. NT3-chitosan, when inserted into a 5 mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous neural stem cells forming functional neural networks, which interconnected the severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis by NT3-chitosan could be a novel strategy for treatment of SCI.

                      ABSTRACT

                      Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.
                      Last edited by GRAMMY; 06-08-2018, 10:46 PM.
                      http://spinalcordresearchandadvocacy.wordpress.com/

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