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    First evidence that chitosan could repair spinal damage

    Chitosan offers hope for spinal injury patients

    Richard Borgens and his colleagues from the Center for Paralysis Research at the Purdue School of Veterinary Medicine have a strong record of inventing therapies for treating nerve damage. From Ampyra, which improves walking in multiple sclerosis patients to a spinal cord simulator for spinal injury victims, Borgens has had a hand in developing therapies that directly impact patients and their quality of life. Another therapy that is currently undergoing testing is the use of polyethylene glycol (PEG) to seal and repair damaged spinal cord nerve cells. By repairing the damaged membranes of nerve cells, Borgens and his team can restore the spinal cord's ability to transmit signals to the brain. However, there is one possible clinical drawback: PEG's breakdown products are potentially toxic. Is there a biodegradable non-toxic compound that is equally effective at targeting and repairing damaged nerve membranes? Borgens teamed up with physiologist Riyi Shi and chemist Youngnam Cho, who pointed out that some sugars are capable of targeting damaged membranes. Could they find a sugar that restored spinal cord activity as effectively as PEG? Borgens and his team publish their discovery that chitosan can repair damaged nerve cell membranes in The Journal of Experimental Biology on 16 April 2010 at http://jeb.biologists.org.

    http://www.eurekalert.org/pub_releas...-fet040810.php

    Having initially tested mannose and found that it did not repair spinal cord nerve membranes, Cho decided to test a modified form of chitin, one of the most common sugars that is found in crustacean shells. Converting chitin into chitosan, Cho isolated a segment of guinea pig spinal cord, compressed a section, applied the modified chitin and then added a fluorescent dye that could only enter the cells through damaged membranes. If the chitosan repaired the crushed membranes then the spinal cord tissue would be unstained, but if the chitosan had failed, the spinal cord neurons would be flooded with the fluorescent dye. Viewing a section of the spinal cord under the microscope, Cho was amazed to see that the spinal cord was completely dark. None of the dye had entered the nerve cells. Chitosan had repaired the damaged cell membranes.

    Next Cho tested whether a dose of chitosan could prevent large molecules from leaking from damaged spinal cord cells. Testing for the presence of the colossal enzyme lactate dehydrogenase (LDH), Borgens admits he was amazed to see that levels of LDH leakage from chitosan treated spinal cord were lower than from undamaged spinal cords. Not only had the sugar repaired membranes at the compression site but also at other sites where the cell membranes were broken due to handling. And when the duo tested for the presence of harmful reactive oxygen species (ROS), released when ATP generating mitochondria are damaged, they found that ROS levels also fell after applying chitosan to the damaged tissue: chitosan probably repairs mitochondrial membranes as well as the nerve cell membranes.

    But could chitosan restore the spinal cord's ability to transmit electrical signals to the brain through a damaged region? Measuring the brain's response to nerve signals generated in a guinea pig's hind leg, the duo saw that the signals were unable to reach the brain through a damaged spinal cord. However, 30·min after injecting chitosan into the rodents, the signals miraculously returned to the animals' brains. Chitosan was able to repair the damaged spinal cord so that it could carry signals from the animal's body to its brain.

    Borgens is extremely excited by this discovery that chitosan is able to locate and repair damaged spinal cord tissue and is even more enthusiastic by the prospect that nanoparticles of chitosan could also target delivery of neuroprotective drugs directly to the site of injury 'giving us a dual bang for our buck,' says Borgens.

    ###

    IF REPORTING ON THIS STORY, PLEASE MENTION THE JOURNAL OF EXPERIMENTAL BIOLOGY AS THE SOURCE AND, IF REPORTING ONLINE, PLEASE CARRY A LINK TO: http://jeb.biologists.org

    REFERENCE: Cho, Y., Shi, R. and Borgens, R. B. (2010). Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury. J. Exp. Biol. 213, 1513-1520.

    This article is posted on this site to give advance access to other authorised media who may wish to report on this story. Full attribution is required, and if reporting online a link to jeb.biologists.com is also required. The story posted here is COPYRIGHTED. Therefore advance permission is required before any and every reproduction of each article in full. PLEASE CONTACT permissions@biologists.com

    THIS ARTICLE APPEARS IN THE JOURNAL OF EXPERIMENTAL BIOLOGY ON: 16 April 2010. EMBARGOED UNTIL FRIDAY, 16 April 2010, 00.15 HRS EDT (05:15 HRS BST)

    #2
    Sea-shells seem a pretty surprising source for cure material but this sounds extremely interesting.

    http://www.telegraph.co.uk/health/he...-research.html

    Comment


      #3
      Originally posted by carbar View Post
      Sea-shells seem a pretty surprising source for cure material but this sounds extremely interesting.

      http://www.telegraph.co.uk/health/he...-research.html
      agreeed..

      Comment


        #4
        Oh well
        Last edited by Skogy; 16 Apr 2010, 12:27 PM.

        Comment


          #5
          Originally posted by carbar View Post
          Sea-shells seem a pretty surprising source for cure material but this sounds extremely interesting.

          http://www.telegraph.co.uk/health/he...-research.html
          carbar,

          Please understand that this is something that is applied to acute spinal cord injury. It is a neuroprotective therapy.

          This is also not the "first" evidence. This material has been around and available in China for some time. I also believe that this was the material that Kunming neurosurgeons were using when they were transplanting fetal Schwann cells into the spinal cord of people with subacute and chronic spinal cord injury. When I first observed their surgery several years ago, I had noticed that they were pouring clear material onto the spinal cord before closing the dura. They showed me a bottle with a label indicating that this is a protein solution called Chitosan.

          Wise.

          Comment


            #6
            No further development of this therapy?

            Comment


              #7
              Originally posted by Wise Young View Post
              carbar,

              Please understand that this is something that is applied to acute spinal cord injury. It is a neuroprotective therapy.

              This is also not the "first" evidence. This material has been around and available in China for some time. I also believe that this was the material that Kunming neurosurgeons were using when they were transplanting fetal Schwann cells into the spinal cord of people with subacute and chronic spinal cord injury. When I first observed their surgery several years ago, I had noticed that they were pouring clear material onto the spinal cord before closing the dura. They showed me a bottle with a label indicating that this is a protein solution called Chitosan.

              Wise.

              Wise,
              I had gathered that it was for 'acute' application but that doesn't make me any less interested in it. And if it is replicating the work done in China AND proves to be effective and safe, then it is even more encouraging and may possibly go further towards becoming a treatment for acutes.

              Comment


                #8
                Originally posted by KIM View Post
                No further development of this therapy?
                I think that this is an interesting report of Chitosan's effect on acutely injured cells. There needs to be more studies to show that there is no immune reaction to this foreign protein. This, by the way, is a foreign protein and it is likely that the FDA will require safety studies to indicate that people do not have an immune or allergic response to the protein. I have not see the paper yet but I am not quite sure how this would be given to the spinal cord. In China, this material is being put directly onto the spinal cord of people. Unfortunately, there has never been a controlled study and therefore we don't know whether it improves recovery or not.

                Wise.

                Comment


                  #9
                  Originally posted by carbar View Post
                  Wise,
                  I had gathered that it was for 'acute' application but that doesn't make me any less interested in it. And if it is replicating the work done in China AND proves to be effective and safe, then it is even more encouraging and may possibly go further towards becoming a treatment for acutes.
                  Carbar,

                  Please understand that I did not say that it is not interesting. I just wanted people to know that this is only for acute spinal cord injury and that it is not new. I first heard of Chitosan in 2004 and think that it was around before that time. I have seen it applied to human spinal cords during transplantation and don't think that it is producing big differences in recovery. Safety studies still have to done to ensure that it does not produce immune responses.

                  Wise.

                  Comment


                    #10
                    Interesting. I'm sitting in front of a bottle of Chitosan plus right now that I had bought a number of years ago. It was promoted as a weight loss suppliment. I just checked out the expiration date, it was 1999, lol. Had it in cabinet all these years. I thought that "Chitosan" sounded familiiar. Sure enough thats what I have. Still have about 100 pills left. I'm sure probabley tonight I'll have a dream I start taking these pills and am walking within a few weeks.
                    "Life is about how you
                    respond to not only the
                    challenges you're dealt but
                    the challenges you seek...If
                    you have no goals, no
                    mountains to climb, your
                    soul dies".~Liz Fordred

                    Comment


                      #11
                      Originally posted by Curt Leatherbee View Post
                      Interesting. I'm sitting in front of a bottle of Chitosan plus right now that I had bought a number of years ago. It was promoted as a weight loss suppliment. I just checked out the expiration date, it was 1999, lol. Had it in cabinet all these years. I thought that "Chitosan" sounded familiiar. Sure enough thats what I have. Still have about 100 pills left. I'm sure probabley tonight I'll have a dream I start taking these pills and am walking within a few weeks.
                      ...not few weeks, don't you know the story of 5 more years?
                      In God we trust; all others bring data. - Edwards Deming

                      Comment


                        #12
                        I wonder if they can bypass FDA approval like the other guys that do the bone marrow stem cell injections... Isn't this like the same stuff Chondroitin thats sold over the counter for joint issues as a supplement?

                        Comment


                          #13
                          Originally posted by Curt Leatherbee View Post
                          Interesting. I'm sitting in front of a bottle of Chitosan plus right now that I had bought a number of years ago. It was promoted as a weight loss suppliment. I just checked out the expiration date, it was 1999, lol. Had it in cabinet all these years. I thought that "Chitosan" sounded familiiar. Sure enough thats what I have. Still have about 100 pills left. I'm sure probabley tonight I'll have a dream I start taking these pills and am walking within a few weeks.
                          Curt, this is a first. You didn't know that you had a "cure" sitting in your bathroom cabinet for ten years. Wikipedia has quite an extensive article on it and its various uses, including horticulture and water filtering.

                          http://en.wikipedia.org/wiki/Chitosan
                          Chitosan is produced commercially by deacetylation of chitin , which is the structural element in the exoskeleton of crustaceans (crabs, shrimp, etc.) and cell walls of fungi. The degree of deacetylation (%DD) can be determined by NMR spectroscopy, and the %DD in commercial chitosans is in the range 60-100 %.
                          The amino group in chitosan has a pKa value of ~6.5, thus, chitosan is positively charged and soluble in acidic to neutral solution with a charge density dependent on pH and the %DA-value. This makes chitosan a bioadhesive which readily binds to negatively charged surfaces such as mucosal membranes. Chitosan enhances the transport of polar drugs across epithelial surfaces, and is biocompatible and biodegradable. Purified qualities of chitosans are available for biomedical applications.
                          Chitosan and its derivatives such as trimethylchitosan (where the amino group has been trimethylated) have been used in non-viral gene delivery. Trimethylchitosan, or quaternised chitosan, has been shown to transfect breast cancer cells; with increased degree of trimethylation increasing the cytotoxicity and at approximately 50% trimethylation the derivative is the most efficient at gene delivery. Oligomeric derivatives (3-6 kDa) are relatively non-toxic and have good gene delivery properties.[2]
                          The Wikipedia article also says that Chitosan is hypoallergenic, has anti-bacterial properties, and is being used by the U.S. Army on the battlefields of Iraq. It apparently also absorbs fat, the reason you may have it in your cabinet.

                          Biomedical use
                          Chitosan's properties allow it to rapidly clot blood, and has recently gained approval in the United States for use in bandages and other hemostatic agents. Chitosan purified from shrimp shells is used in the range of hemostatic products. Chitosan hemostatic products have been shown in testing by the U.S. Marine Corps to quickly stop bleeding and result in 100% survival of otherwise lethal arterial wounds in swine and to reduce blood loss.[31] Chitosan hemostatic products reduce blood loss in comparison to gauze dressings and increase patient survival.[32] Chitosan hemostatic products have been sold to the U.S. Army, who have already used the bandages on the battlefields of Iraq.[33] Chitosan is hypoallergenic, and has natural anti-bacterial properties, further supporting its use in field bandages.[34]
                          There was also a recent paper published on its use to repair injured spinal cords and as a scaffold for stem cells. I attach the papers. What it is getting more and more interesting...

                          Wise.

                          Comment


                            #14
                            Originally posted by XYNaPSE View Post
                            I wonder if they can bypass FDA approval like the other guys that do the bone marrow stem cell injections... Isn't this like the same stuff Chondroitin thats sold over the counter for joint issues as a supplement?
                            If the material is to be injected into the spinal cord, it will require animal safety data (if the data is not already available). Chitosan has been around for a long long time. I of course knew about chitin because this is the material that shrimp shells are made from but I wasn't aware of the all the biomedical uses of this material. By the way, what one eats is very different from what one injects into the body and particularly into the spinal cord.

                            Wise.

                            Comment


                              #15
                              I know chitosan has been used for a while for many tissue engineering applications as a popular biomaterial, so I believe its biocompatibility is well established. I saw recently its use in hydrogel form for pancreatic islet encapsulation and also I heard it stimulates some kind of bone remodeling when used as a scaffold. But also the article mentions that PEG could be toxic, I never heard about that. People use it all the time to coat things because it is less immunogenic than something like chitosan.

                              Comment

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