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    Originally posted by GRAMMY View Post
    When will the Cethrin chronic rat study be scheduled in the lab?
    What combination would be added other than aspirin for those chronic rats?
    Maybe Motrin?

    Comment


      lol - I have taken hundreds of bottles of Motrin over the years for PMS, pain, headaches, etc.

      No improvements here.
      Roses are red. Tacos are enjoyable. Don't blame immigrants, because you're unemployable.

      T-11 Flaccid Paraplegic due to TM July 1985 @ age 12

      Comment


        Originally posted by nrf View Post
        Maybe Motrin?
        Humm...I guess I wouldn't expect anything to develop with an ibuprofen chronic rat study anytime soon. Wise's Cethrin chronic rat study hasn't even been started yet. I'd just thought the basic lab work was probably underway by now. I'm anxious to see the results of his chronic rat studies with Cethrin. I hope it gets put on the lab schedule real soon.
        http://spinalcordresearchandadvocacy.wordpress.com/

        Comment


          "should be investigated further", "It should be studied", "it should be done", "it would be reasonable" Wisy man.
          Wise, you are just one big "Shouldy-Wouldy".

          Comment


            Originally posted by ay2012 View Post
            Hmmm...isn't that quite an atheoretical statement? No disproving empirical evidence surely isn't the only criteria in testing a potential therapy.....
            ay2012,

            There is strong evidence that Indomethacin and Ibuprofen (and aspirin) block RhoA. We know that RhoA is the intracellular messenger that mediate the effects of axon growth inhibitory signals, like Cethrin. Fu, et al. reported that Indo and Ibu both stimulate axonal growth in culture, in the presence of myelin and other inhibitors of axonal growth.

            In fact, the data suggest that Ibuprofen and Indomethancin are each more effective in reducing active RhoA than Cethrin, both in culture and in lesioned rat spinal cords. In injured spinal cords, RhoA activity increases significantly and this may be because axons and cells are encountering CSPG and other molecules that are activating RhoA. Ibuprofen or Indomethacin blocks this increase. Naproxen, another NSAID, does not.

            Finally, when they gave Ibuprofen to rats that had dorsal hemisections, they found regeneration of corticospinal and serotonergic tracts. In control (untreated) animals, only a few BDA (this is a dye that is injected into the motor cortex) labelled corticospinal tracts grew across the injury site. However, in Ibuprofen treated rats, they found many BDA-labelled axons distal to the injury site. They also found increased growth of seronergic (5-HT) axons. These axons grew fairly long distances beyond the injury site (>10 mm).

            It is true that relatively high doses of these two drugs are required to block RhoA completely. For example, ibuprofen has to be given at 50-62.5 mg/kg/day (compared to normal clinical doses of 15 mg/kg/day). The safety and required duration of such doses is not clear. They also starting giving the drug (by subcutaneous pump) shortly after injury. It may be better to deliver the drugs directly to the spinal cord than to give the drugs systemically for weeks or months, since such high doses of drugs may have side-effects.

            Fu, et al. reported that the treatment improves BBB scores from 13 to 15. I have already commented on this, saying that BBB scores may not be valid when used to assess dorsal hemisection. The study is not perfect but it provided substantial data indicating that ibuprofen and indomethacin strongly inhibit RhoA activation. In fact, it does so better than Cethrin. It is seriously being considered by many laboratories as a therapy to include in various combination therapies.

            I am dismayed to hear all these disparaging remarks about this work because it is using two common drugs. I wonder if most people here have even read the paper before they dismissed the therapy. I am disappointed that people would choose to make insulting remarks to people who are saying that the treatment should not be dismissed and should be studied further.

            Wise.
            Last edited by Wise Young; 9 Feb 2013, 6:53 AM.

            Comment


              Originally posted by GRAMMY View Post
              Humm...I guess I wouldn't expect anything to develop with an ibuprofen chronic rat study anytime soon. Wise's Cethrin chronic rat study hasn't even been started yet. I'd just thought the basic lab work was probably underway by now. I'm anxious to see the results of his chronic rat studies with Cethrin. I hope it gets put on the lab schedule real soon.
              We have not received any Cethrin yet for the studies. Wise.

              Comment


                I wrote to Professor Strittmatter veiled the responses

                Dear Mr. Partick Guerdner,
                Sorry to hear of your injury. In our laboratory animal studies, Ibuprofen was effective for improving outcome of recent spinal cord injuries (less than one week), but turned out to be ineffective for chronic injuries (older than 3 months).
                Best regards,
                Steve Strittmatter


                The chronic ibuprofen data has not been published.
                We are working to a human clinical trail in chronic SCI with NgR-Fc. The work now is completing protein production in large amounts to FDA standards adn completing toxicology studies. We hope to start in the clinic within 18-24 months.
                Best
                Steve

                Comment


                  Originally posted by Wise Young View Post
                  Pelican,

                  I agree that people should not be popping ibuprofen or indomethacin. On the other hand, that is not a reason to dismiss these findings as being bogus or unimportant. The results are significant and should be investigated further.

                  Wise.
                  I didn't dismiss anything as being bogus. But I do question the rationale to take this to human trials without compelling evidence in a clinically relevant animal injury model. The fact that human trials are incredibly expensive to execute and difficult to recruit for should mean that the selection criteria of therapies for human trials should be very carefully and efficiently thought out.

                  Obviously the goal of Cure is important, but equally important is the critical path to goal with the resources available to the clinical community. Cash is king, and the custodians of the cash need to take a balanced approach in selecting therapies during frugal times. You always want the "biggest Bang for your Buck". A scattergun approach raises the probability of failure - and impacts the argument that investing in science to reduce healthcare costs diminishes - especially when governments are making huge cutbacks.

                  Comment


                    Where will the bar be set for success in the chronic animal studies using Cethrin? Since UCBMC can't be tested on the animals, will it be shown that Cethrin alone causes regeneration and return of function in a chronic severe contusion model before moving forward with the plan to test it in the clinical trial network?

                    Comment


                      Originally posted by kivi66 View Post
                      "should be investigated further", "It should be studied", "it should be done", "it would be reasonable" Wisy man.
                      Wise, you are just one big "Shouldy-Wouldy".
                      Hmm..
                      Originally posted by kivi66 View Post
                      Dr.Silver, does Wise's HLA-matching theory as a hurdle for conducting pig trials make sence to you?
                      What about your own collaboration with pig-oriented labs?
                      Wise is perfoming trials, you are just ctiticise him.
                      If you continue with not-replying to me, then your transformation into "stephen davies" has begun.
                      Jerry, pigs are your best friends for now. And I am very serious by saying that.

                      Comment


                        Originally posted by lynnifer View Post
                        lol - I have taken hundreds of bottles of Motrin over the years for PMS, pain, headaches, etc.

                        No improvements here.
                        There is no possible way, post-hoc, to gauge if ibuprofen had anything to do with your improvements or not. It should be studied in a clinical trial.

                        Originally posted by lynnifer View Post
                        I'm kind of caught in the middle here because there are some of us 20yrs+ who have experienced a sort of 'spontaneous regeneration' as Dr Young calls it ... I know I experienced it myself before the Ampyra came along (and greatly improved things). Dr Young claimed he had a friend that this happened to as well after decades.

                        My left abdomen below the navel came back in a patch after I work up from some unrelated surgery. Eight years later that area expanded by an inch or so, down and across.

                        I'm the anomaly with Transverse Myelitis though as I don't know enough about how these research options will or will not help me.

                        Comment


                          Originally posted by Fly_Pelican_Fly View Post
                          Good luck finding a principal investigator, the venture capital and a trial infrastructure for this incredibly awesome idea!
                          Even though I sense sarcasm here, I agree with your point.
                          “Yet a proper, randomized clinical trial has never been done because no company wants to pay for an ibuprofen trial when it can be bought in [a store] for five cents a pill,” McGeer said.

                          “The cheaper the agent, the less the incentive to fund expensive clinical trials,” he said, referring to the fact that pharmaceutical companies only want to sponsor research on new drug agents they can patent and can profit from.

                          Comment


                            Originally posted by crabbyshark View Post
                            Hmm..
                            crabby, I've put things right in the researchblog-thread.

                            Comment


                              Originally posted by crabbyshark View Post
                              “Yet a proper, randomized clinical trial has never been done because no company wants to pay for an ibuprofen trial when it can be bought in [a store] for five cents a pill,” McGeer said.

                              “The cheaper the agent, the less the incentive to fund expensive clinical trials,” he said, referring to the fact that pharmaceutical companies only want to sponsor research on new drug agents they can patent and can profit from.
                              Based on the very nature of its financial resources, a non-commercial clinical trial (network) should be taking less risk than a commercial clinical trial run by a large biotech or pharmaceutical when selecting a therapeutic target. Larger entities can afford the odd failure. Non-commercial trials cannot afford failure when money is so hard to come by. All the more reason for demonstrating compelling evidence in the translational stage in a clinically relevant chronic animal model before moving forward with any trial. Dont you think?

                              Comment


                                This thread has gone downhill.

                                I've tried to stay out of the China one now that there's a separate one.

                                Funny how the mods aren't 'moderating' this one as heavily as they were Dr Young's ... but that's how it is around here.
                                Roses are red. Tacos are enjoyable. Don't blame immigrants, because you're unemployable.

                                T-11 Flaccid Paraplegic due to TM July 1985 @ age 12

                                Comment

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