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Thread: Jerry Silver and Other Discussion from ChinaSCINet Update

  1. #421
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    Quote 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?

  2. #422
    Senior Member lynnifer's Avatar
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    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

  3. #423
    Quote 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.

  4. #424
    "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".

  5. #425
    Quote 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; 02-09-2013 at 06:53 AM.

  6. #426
    Quote 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.

  7. #427
    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
    JustaDollarPlease.org

  8. #428
    Quote 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.

  9. #429
    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?

  10. #430
    Quote 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..
    Quote 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.

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