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Thread: Regeneration vs Cell Replacement Therapies

  1. #81
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    Oh No!!!

    You are telling me that the leading scientists of this world are working on a cure for people who are injured ONLY 10 days or less after substaining a sci???

    You have got to be kidding me!

    Unless i have lost my ever loving mind, i thought that we would work towards finding a cure for those that are currently suffering, not take baby steps, just for the sake of money!!! OMG!!!!

    Egnorance is bliss. The more i learn the more i become aware of the awefulness in which science is handled for the sake of science..
    i am in tears....

    I offer you money. Tell me what you need and i can get it to you, but please, give us back our freedom~.

    Gods speed....
    Susan

  2. #82
    I feel the same way Superstar. I believe if we find the "cure" however it may be defined, scientists must have a balance of studying the mechanisms that will heal us in a chronic injury and in an acute model. We need more funding and support to help the scientists to be able to achieve this balance to end our suffering. Superstar I applaud you in your tenacious efforts, your name says it all. I also applaud scientists for working with the best they have, but they need more public and financial support. This is just coming from a person who so badly wants to be out of this chair as the rest of us do. I hope I am correct in my assumptions.

    JOE

  3. #83
    Guys, most therapies are tested in acutes first, it doesn't mean they won't work in chronics. As I tried to explain earlier, researchers choose the route of least risk to prove efficacy. Positive results in acutes will ensure future funding. If a study fails in acutes, the likihood of it being tested on chronics is low. Acutes studies are a necessary first step to a cure for chronic injuries.

  4. #84
    Susan,

    We are working on rolipram, db cAMP and OEG transplants in acute and chronic spinal cord injury. The experiments are going on. I don't know the results of the study because we do not unblind the study until it is completed.

    In the meantime, rolipram was recently tested in clinical trial for multiple sclerosis. This trial has been going on since 2002 and was recently completed (April 2004). The results have not yet been published. The trial is described in a topic in the Clinical Trials Forum.

    Rolipram is first developed by the company Schering AG and subsequently licensed to Berlex Laboratories and Meiji Seika Kaisha but apparently there is some reluctance of the companies to invest in developing the drug even though there is strong interest in the drug for treating AIDS and other inflammatory conditions. A 1996 article suggested that AIDS groups have put some pressure on the companies to fund a clinical trial of the drug in AIDS http://www.aids.org/atn/a-242-03.html

    Marie Filbin and colleagues recently reported that rolipram when started 2 weeks after a hemisection of C3/4 in rats resulted in reduction of gliosis, increased axonal growth, and functional recovery.

    There are currently many ongoing studies of rolipram on immune responses in animals. Rolipram is approved in Japan and some European countries for the treatment of depression. Its main side effect is nausea. Incidentally, as an anti-depressive, a 1989 study suggest that rolipram is not as effective as imipramine in treating depression.

    Wise.

  5. #85
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    thanks Dr. Young for the response!

    when will the treatments be finished and how soon until we will know the results?

    Also, i am a bit confused about the blind ways of doing things... If the rat walks, then this is a a scientific miracle!

    Gods speed~
    Susan

  6. #86
    Susan,

    We usually unblind when all the data has been collected and analyzed. Chronic spinal cord injury experiments take a long time. We have to keep a rat 12 weeks before we inject tracers into the brain and another 2 weeks to allow the tracers label the axons. If we injured 8 rats a week for the experiment (that is a lot) and there were 80 rats in the experiment, it takes about 10 weeks plus 14 weeks, a total of about 6 months. Usually we know within a week or so after the exepriment ends, whether the rats are walking better. The rats are scored every week. The histological analysis takes several months. So, a typical chronic experiments takes about 9 months to collect and analyze the data.

    If the experiments are not carefully done, the control rats will recover more or less walking than they should. The investigators really really want the rats to walk, especially after they have worked months and months on the treatment. Therefore, the people who are scoring rat walking don't know which treatments the rats received. On big and complicated experiments, we often do what I call a half-way analysis. We do half the experiment and unblind to see if there are any trends in mortality and walking changes. Depending on a priori criteria, we either stop or complete the experiment. From the viewpoint of statistics, such "half-way" peeks at the data reduces the "power" and we have to do a few more animals per group to achieve statistical significance.

    You would be surprised at how much people (including myself) want data to be positive. It is not difficult to be biased when scoring walking, perhaps looking a little bit harder or longer for clues of walking... etc.

    Spinal-injured rats are carefully inspected twice daily by our animal care team and receive bladder urine expression (we don't catheterize them). At the first sign of infection, we need to start antibiotics. If the rats bite themselves (a possible sign of neuropathic pain), we have to stop it. In addition, since most of the experiments involve cell transplants, we usually give the rats daily injections of cyclosporin (immunosuppressant). When a rat dies before the end of the experiment, people are really sad and there is extensive discussion of what went wrong and why. Our animal care team has less than 5% 12-week mortality of spinal-injured rats and is proud of this accomplishment.

    Wise.

    [This message was edited by Wise Young on 08-18-04 at 10:57 AM.]

  7. #87
    Thanks for the info Dr. Young. How many chronic injury experiments do you have currently ongoing? When will each be complete? and when will you be able to share the results?

    Finally, MP said they needed to try their combo treatment on chronically injured rats. Do you know the status of those experiments and when we may get some insight into the results? Needless to say alot of us are waiting anxiously to see if it is as effective on the chronic injury.

  8. #88
    Quadfather, we started the OEG transplants to chronic spinal-injured rats sometime in February and hope to have those results in the next month or so. We started the rolipram+dbcAMP studies in acute spinal cord injury first to make sure that we are doing the procedures correctly and encountered difficulties showing the rolipram + db cAMP increases cAMP levels in the spinal cord. We have started a small series of OEG + rolipram + db cAMP on acute injuries. We are just getting ready to start doing it in chronic spinal cord injuries.

    Due to funding and personnel limitations, we have had to schedule the experiments over a longer period that we would like. At the present, we have four full-time animal care people who work very hard caring for a colony of 150 chronic spinal injured rats. By the way, just so that people understand keeping a colony of 150 spinal-injured rats entails, think of having to express the bladders of 150 rats twice a day. If it takes 5 minutes per rat, one person can just do 12 rats per hour. This is in addition operating on the rats, grading each of the rats for locomotor function every week, euthanizing them, sectioning their spinal cords for histological analyses, and analyzing the data.

    By the way, we have several other major experiments going on. These include:
    1. finding out why OEG transplants are producing such rapid recovery when transplanted into chronically injured spinal cords. We have seen rapid recovery in the rats similar to what Dr. Huang has seen in humans.
    2. Combination therapies using stem cells combined with the L1 cell adhesion molecule or chondroitinase.
    3. Injecting chondroitinase into rats with chronic spinal cord injury.
    4. Growing and transplanting umbilical cord blood stem cells in acute and chronic spinal cord injury

    We have been juggling our schedule and working as hard as we can. Assuming that everything goes well, I hope to report some findings in San Diego (October).

    Wise.

    [This message was edited by Wise Young on 08-18-04 at 11:48 AM.]

  9. #89
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    Thank you Dr. Young....

    Please find us a cure.

    I know you are trying *very* hard and i and many others are very grateful for your hard work with your rats.

    This made me grin when Wise said...
    "You would be surprised at how much people (including myself) want data to be positive. It is not difficult to be biased when scoring walking, perhaps looking a little bit harder or longer for clues of walking... etc.

    Gods speed~
    Susan

  10. #90
    Dr. Wise,
    What a great explanation..one almost feels like they are witnessing these events. (well almost)

    When you injure the rats exactly presumably
    in the exact manner..do all the rats present
    the exact same paralysis?

    Do your injured rats have to physically
    move to have a bowel movement like our dogs do?

    Do the rats get drag sores on their limbs like our dogs do? If not how do you prevent
    them from forming.

    How do you test the rats for sensory and pain
    perception?

    And how small is their spinal canal and their spinal cord?

    How difficult it must be to work on something
    so little and intricate at the same time.
    God Bless you and your rodents.

    Help is on the way.

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