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Go for Novartis Nogo trial

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    Go for Novartis Nogo trial

    Based on successful Nogo antibody trials on monkeys and rats, an international clinical trial with 50 - 100 acute SCI patients is the next step (summary of an article in the Unimagazin of the Univ. of Zurich - see page 8).

    Martin Schwab said that 6 experts of Novartis optimized and tested the Nogo antibody (for safety and dosage optimum) on monkeys for 5 years. The University of Zurich is the patent holder, Novartis has the marketing license. Once the new antibody is proven safe, it will most likely be a great component in combination with cell transplants. To my knowledge, animal experiments with the Nogo antibody in combination with autologous stem cells and OEG-cells have been performed for a couple of years already.

    Links to Novartis Instiutes for Biomedical Research
    The Nogo project is featured under "Disease Area" Neuroscience (seems to be a 2003 article):

    To my knowledge, animal experiments with the Nogo antibody in combination with autologous stem cells and OEG-cells have been performed for a couple of years already.
    I assume these combo experiments would also be aimed at the acute phase of injury also?



      The predecessor antibody IN-1 was already tested on chronic rats and I was told that the rats recovered, but not to the same degree as the acute rats did. The conclusion was, applying the Nogo antibody alone, was quite efficient in light contusion injuries because the nerves grew along the scar using it as a scaffolding.

      But Martin Schwab and most experts agree that the ultimate cure will be a combination of (this was said in the article) cell transplants to "repair" the lesion and jump-start axon growth, whereas the Nogo antibody's function will be to keep the axons growing until they reach their counterparts. Therefore, a combination therapy will be the optimum for both, the acute and the chronic injury.

      I bet you if Dr. Huang could apply the Nogo antibody after the OEG transplantation, the degree of recovery would be tremendous.



        Thank you. Fascinating. I have read about Nogo in Luba Vikhanski's "In Search of the Lost Cord".

        I wonder if:

        <LI>Nogo and it's clinical trial results will available anytime in the near future for other clinicians to use (such as Dr. Huang)?
        <LI>Nogo's therapeutic benefits will be presented this December at the HKU-SCi symposium?

        Lastly, you indicated "a combination therapy will be the optimum for both, the acute and the chronic injury", however, the upcoming trial is for acutes only.

        Just wondering why?


          Schmeky, Why

          My guess is money, they need to do what will show the best results the quickest and their bet is thats acutes. sucks

          "All you have to decide is what to do with the time that is given you."
          Gandolf the Gray

          2010 SCINet Clinical Trial Support Squad Member

          "You kids and your cures, why back when I was injured they gave us a wheelchair and that's the way it was and we liked it!" Grumpy Old Man

          .."i used to be able to goof around so much because i knew Superman had my back. now all i've got is his example -- and that's gonna have to be enough."



            Regarding the availability of Novartis' Nogo antibody, I don't have a clear view of what Novartis' marketing strategy is all about. Needless to say that they want to make a lot of money with the antibody, since it also works for brain injuries (which is about 5-10 times more frequent than SCI and brain strokes - about 20 times as frequent as SCI).

            Their goal must be to bring the product to the global market asap, but without sacrificing safety (similar to their cancer drug "Glivec").
            I mean testing the substance for 5 years on monkeys tells me that safety is their #1 priority. According to Prof. Schwab, they even optimized the dosage - never heard about that before.

            Maybe Dr. Young could read more out of their "bench to bed" approach and give us an idea what kind of strategy Novartis is pursuing.

            Regarding your second thought - I think it'll take a year before they present any preliminary data of the trial. The rules in the EU are similar to the FDA rules in the US. Again, maybe Dr. Young knows when and what kind of data of a clinical trial a company is allowed to present to the public.

            Your last question: Prof. Schwab and Lisa Schnell indicated that a combo therapy will be the ultimate cure for SCI.

            The reason why they have to start with acute injuries is a necessity which comes from the regulation of the health authorities of Switzerland and the EU (EMEA).
            This is the rule: if Novartis treated acute injured monkeys, they have to test it first for safety on acute injured humans - it's as simple as that.

            Yet, it needs to be pointed out that Prof. Schwab said in the article, that they are working on a cure for CHRONIC SCI, too. For example, Prof. Christine Bandtlow who was a co-worker of Schwab for 12 years, got a professorship at the Innsbruck University. There she has been using the antibody in combination with autologous stem cells in animal experiments for a couple of years.

            The rehab center Balgrist (Zurich) is in charge of the international multicenter trial. I assume that they'll treat a few patients in Balgrist (safety), before they permit the other centers (Bayreuth, Heidelberg, Nijmegen and Paris) to start with their trial.

            If you want more information, mail to Dr. Anita Buchli - she is in charge of distributing information about the trial:

            In my opinion, those doctors (such as Drs. Huang and Lima) who have already substantial cell transplant experience with humans will benefit the most from adding the new drug to their cell transplant therapies.


              willfried, thank you very much for posting this information. Wise.



                Thank you very much for such insightful information. You appear to have a keen grasp of what these researchers are doing.

                Safety should be a primary concern when you are applying anything to the Central Nervous System. 5 years if testing should prove safety.

                The fact they are working on a cure for chronics is encouraging. I agree with your analogy of Huang and Lima already having experience in the cell transplant area. They need to suppliment their efforts with additional interventions when sufficient data proves efficacy.

                Please keep us informed.


                  I have some additional info.
                  I know the NOGO-antibody has been tested in combination with NT-3 long ago and it improved the results. In 2003 they were, together with 2 foreign labs, also testing it in combination with Chondroitinase ABC but I don't have the definite endresults of that trials.
                  And although you would probably expect that a NOGO-antibody causes long distance axon regeneration (as Wilfried pointed out), the initial results from the monkey trials seemed to indicate that the NOGO-antibody mainly resulted in sprouting of existing axons rather than (long distance) axon regeneration.
                  I've also been told that they would start with thoracal injuries and that their intention was to involve chronic injuries in phase 2 if everything went well. But I haven't contacted them for 1,5 year so maybe their plans are changed.


                    Hello Peter,

                    Regarding the regeneration mechanism, I didn't want to imply that Nogo antibodies cause long-distance growth. That would mean that a high-level chronic SCI patient would need the antibody treatment for up to a year or even longer.

                    If I understand the regeneration mechanism right, the Nogo antibody which is directly applied to the spinal cord with a regular Medtronics pump, causes - as you said - the axons to sprout into the cervical pathways where they make "indirect" connections to the lower end of the spinal cord.

                    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 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.



                        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.


                          A complete healing of the spinal cord, will probably never be achieved.

                          Come on now... what happened to us only needing 10%?
                          A good friend is someone who will come to bail you out of jail. A TRUE friend is the guy sitting next to you behind the same set of bars saying, "boy we sure f*cked up this time huh?"


                            Could someone explain false interconnections, and their releation to treating SCI?
                            c6/7 complete


                              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.