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Thread: Go for Novartis Nogo trial

  1. #11
    Senior Member Schmeky's Avatar
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    Sep 2002
    West Monroe, LA, USA
    Wilfried pposted:
    Schwab said, for him the most fascinating discovery of his 20 year research, is the fact, that the axons always made the right connections!
    Wilfried, your information is again, not only fascinating, but useful.

    Please stay with this forum. Your contributions are welcome.


  2. #12
    Here is the translation of the article:

    New hope for paraplegics?

    Can injuries of the spinal cord be partly healed soon? Zurich brain researcher Martin Schwab is testing his treatment on paraplegic humans after it was successful in animal trials.
    Ruth Jahn

    1988 a team of researchers under Martin Schwab, director of the Brain Research Institute of the University of Zurich, discovered a protein, which exists only in the central nervous system where it acts as a stop signal to nerve regeneration. Martin Schwab named the molecule Nogo. It sits in the myelin layer, which covers the nerve fibers in the spinal cord. Schwab's group manufactured a specific antibody, which neutralized the inhibiting effect of Nogo and therefore nerves could grow after an injury again. "I was a first glimmer of hope, a good starting point for a therapy", Schwab remembers. "A complete healing of the spinal cord, however, will probably never be achieved."

    Trials with 50 to 100 paraplegic patients

    The researchers plan to treat in Switzerland and various European hospitals 50 to 100 patients with the Nogo Antibody. Primarily patients with serious injuries of the spinal cord (paralysis of the lower extremities and inner organs) will be accepted. Silvano Beltrametti however, former Swiss ski racer, who had an accident in 2001 and suffered a thoracic spinal cord injury, would not be ideal candidate for the trial. In the first phase, only acute injuries will be accepted for the study. Results from the animal trials indicate that the Nogo Antibody therapy should take place as early as possible, before a scar forms. "However, we are working on developing therapies in the near future for the chronically injured ", insures Schwab.

    Co-operation with Novartis

    A small pump in the liquid area around the spinal cord pumps the Nogo antibody during some weeks to the area of the lesion. The Nogo antibody, necessary for the therapy of humans, has been developed during the last three years by Martin Schwab's group together with researchers of the industrial partner Novartis. The patent holder of the therapy is the University of Zurich, the pharma concern owns the marketing license. For the preparation of the clinical trials, the researchers also closely co-operate with the clinicians of the rehabilitation center Balgrist of the university clinic and different European hospitals.
    At present the members of the hospital network are working to standardize different medical examination methods. This way, the researchers can check and document whether the Nogo antibody therapy holds the expected improvements compared to the spontaneous regeneration or not.

    No false links of nerve cells

    Before the Nogo Antibody may be used with humans, the researchers must guarantee however that no unforeseeable side effects arise. Currently the substance is examined for safety in a final toxicological test with animals. According to Martin Schwab so far no negative side effects could be found. Antibodies in the central nervous system do not exist, however, no harmful autoimmune reaction to Nogo Antibodies could be found: The fear that the anti-bodies beside Nogo could set also other natural proteins out of effect, did not prove to be true in the animal experiments so far. Also there is no indication that false connections between nerve cells arise. If the researchers neutralize Nogo with antibodies, injured nerves grow to the right target and link themselves with the correct partners. " For me that is the most amazing result of our 20-year old research at all: No false interconnections occur!", Schwab emphasizes.

    Treadmill training

    Muscle training affects the growing of the nerves positively. "any treatment of paraplegics with medication must necessarily be accompanied by intensive physiotherapy ", says Martin Schwab. For example with the Laufband-robot at the university clinic Balgrist, developed for paraplegics. A combined treatment, with Nogo Antibodies and another treatment, some scientists believe to achieve an improvement in the future.

    Improving brain plasticity

    Also in the future one will continue to find the brain researcher Martin Schwab working in the laboratory at the Brain Research Institute. There he continues to work with his team on basic research of the nerve regeneration. Martin Schwab and his group work on the mechanism of nerve regeneration and further growth inhibitors in the central nervous system. They are interested in the molecular basis of the (relatively limited) spontaneous healing process in the spinal cord and brain. And finally the scientists examine whether also neurodegenerative diseases or brain injuries could profit from the Nogo Antikoerper therapy. First trials on rats point to the fact that the Nogo Antibody could also help to improve the plasticity in the brain. Thus still intact brain cells could again organize themselves and be a substitute for damaged cells.

  3. #13
    Senior Member Rollin Rick's Avatar
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    Nov 2002
    B ville, New York, USA
    A complete healing of the spinal cord, will probably never be achieved.

    Come on now... what happened to us only needing 10%?

  4. #14
    Could someone explain false interconnections, and their releation to treating SCI?

  5. #15
    Senior Member
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    Jul 2001
    The Netherlands
    Hi Wilfried,
    Sorry for misinterpretating you, I thought when you said that "they keep the axons growing until they reach their counterparts" you were referring with their counterparts to their original connections.
    Dr.Schwab was very excited that the axons always made the right connections. That fact says much about the plasticity of the spinal cord I think because the sprouting nerve fibers all made complete new connections with other axons and circuits in the lower spinal cord which have lost their connection with the brain. And apparantly the new connections take over the right functions(although some functions maybe have to be "re-learned") and also doesn't cause pain/spasm.

  6. #16

    I just found an informative page on Schwab's web site where they explain three types of regeneration mechanisms for acute injuries:

    It seems to me that similar regeneration processes apply in chronic injuries, except for the one process where axons grow through the lesion (= scar in chronic injuries). OEG/stem cells and chondroitinase obviously make the scar permeable - see thread "What is the importance and are there treatments for scar tisues" by Dr. Young.

    I was not only confused about the fact that the regenerative sprouting of axons occurs on the caudal side of the injury, but it wasn't clear to me how the redundant axons would make the right connection to the periperal nerves.

    So I called Dr. Buchli, btw a very friendly Swiss woman, and she said that she has to check the picture again, since the regeneration direction for the motor axons should be descending, whereas the sensory axons would sprout from the caudal side.

    She said that the unused axons (90%) are in sort of "inactive state". As soon as they receive signals, they start to make the right connection to periperal nerves. That's what fascinates Martin Schwab, he could even verify/watch this process of nerve-connecting in vitro.

  7. #17
    Wilfried, what your messages say is that Dr. Martin Schwab team are able (or something very close) to cure acute sci in monkeys? Is it right?

  8. #18
    Senior Member Schmeky's Avatar
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    Sep 2002
    West Monroe, LA, USA

    I wonder if you know how similiar this technique is to the recent claims by Cheng Chih-hung, in Taiwan, see the link below.

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