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Thread: Regeneration vs Cell Replacement Therapies

  1. #61
    Sherman,

    Regeneration is not only a probability, it is an eventuality. For over 10 years, we have known that the spinal cord can regenerate. The obstacles to regeneration have been identified to a large extent and over a dozen therapies have been shown to regenerate the spinal cord. But, just like AIDS, it is not enough to clear one obstacle at a time. We must provide a path for the axons to grow, make sure that they do not stop after they cross the injury site, and maintain their growth for long periods. I also believe that spontaneous regeneration occurs in most people. It may well be the reason why so many people with "incomplete" spinal cord injuries get substantial function back.

    Cell replacement is a more difficult proposition because it entails not only replacement of neurons but regeneration for axons to connect to the new neurons and for the neurons to send axons to the right place. Without regeneration, neuronal replacement will not work. However, I believe that neuronal replacement is happening.

    By the way, the fact that we cannot replace neurons right now does not mean that regeneration will not benefit people with neuronal damage. Regenerative therapies should restore some function to people. In previous postings, you have complained bitterly of not being able to feel. One of the most interesting aspects of the OEG transplant studies going on around the world is that it can restore some sensory function below the injury site. This alone should be beneficial to many people.

    It is so important that we don't fall into the trap of thinking that research and therapies are not worthwhile unless they cure. Sometimes the mundane treatments can have enormous benefits. For example, drugs that reduce spasticity without causing weakness (e.g. 4-aminopyridine) or that take the edge off of neuropathic pain (e.g. gapapentin) would make a difference to the lives of millions of people. Likewise, treatments that restore bone strength, reverses muscle atrophy, and controls autonomic dysreflexia during sexual activities are important to the lives of people with spinal cord injury (and many other conditions).

    We are suffering from a catastrophic failure of imagination. If all that we can imagine is fearful scenarios of continuing paralysis and pain, that is what will happen. There are so many possibilities that we have not yet begun to explore. For example, why aren't we transplanting inhibitory neurons into the spinal cord to treat neuropathic pain and spasticity, myoblasts to prevent atrophy and rebuild muscle, osteoblasts to restore bone? Why is it that we are still mired in harvesting stem cells rather than growing them or converting any cell of our body into stem cells?

    This is not the first time in history that we have suffered such a catastrophic failure in our imagination. At the turn of past century, there were many who predicted that science had reached its peak. The steam locomotive was believed to be the future. Electricity was just a fanciful toy. Death from infectious disease was considered a matter of course. People then could not imagine the world that we now live in.

    Please, we must not repeat this mistake. We must not allow our poverty of imagination hold us back. The answer to your question is clear. Of course, we will be able to repair the spinal cord and restore function. I know this with surety. It is not a matter of if but a matter of time that we will be able to do it. What we need to do now is to accelerate the process.

    Wise.

  2. #62
    Superstar, as you know, I will do everything that I can to help. Wise.

  3. #63
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    Wise,

    thank you so much!! Just imagining walking and dancing as i once did brings tears to my eyes!

    How do i contact you directly?

    Gods speed and i hope to speak with you soon!!!
    Susan

  4. #64
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    Oh yeah, is there a reason i can not get an answer to this???

    Wise,

    Please help me understand which one of the two statements below is true. Honestly, i am trying to understand everything as quickly as possible and these two statements contradict one another. The reason i ask for an answer is because of the value it holds in terms of what's is going on in the quest for finding a cure using these specific drugs in combination with stem cells.
    thank you..
    Susan

    Ok, i have an important question. Wise, you wrote to me just the other day that and said "There is, to my knowledge, no experience giving rolipram in association with cell transplantation in chronic spinal cord injury (either in human or animals)."

    In the second paragraph of which Seneca posted that says "Wise Young wrote" says, My own group is currently assessing rolipram plus db cAMP plus OEG transplants... similar to the approach taken by Miami Project. We are also studying mechanisms of the early segmental recovery associated with OEG transplants into chronically injured rats, as well as spinal axonal myelination by OEG cells in chronically contused spinal cords.

    Gods speed~

  5. #65
    Senior Member poonsuzanne's Avatar
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    Originally posted by Chris2:


    I think the problems are

    1) The vast majority of sci have been brain washed into "knowing" there is no cure so they accept it and in some cases even celebrate it. This is why there is no uniform protest against the lack of a cure as there was with people with aids.

    2) SCI 'appears' not to be a fatal condition so we merely join what is called the "disabled community"

    3) AB people 'know' it won't happen to them whereas aids, heart attacks, cancer, strokes are things AB's really worry about and therefore rich business people, celebrities, politicians will more likely support those causes.
    Chris, I agree with you entirely!!!

    However, I have never chosen to believe that there will not be a cure forever whatsoever. Therefore...

    Let's, the SCI community, expand our power to smash these obstacles one by one...

    Let's, the SCI community, come together to brain wash every single human being on earth that there will be a cure for SCI...

    Let's, the SCI community, educate people that, "Correct, SCI is not a fatal condition, but, it will unreasonably imprison you for at least forty to sixty years..."

    Let's, the SCI community, reverse the common knowlege that SCI can happen to anyone in a split second, at any time, anywhere, especially commonly to young people...

    Suzanne

    [This message was edited by Suzanne Poon on 08-10-04 at 07:24 PM.]

  6. #66
    superstar,

    I am not sure that I understand what you are asking for. Perhaps I should just comment on what it would take to get OEG transplantation plus rolipram and dibutyryl cAMP into clinical trial.

    Rolipram blocks phosphodiesterase 4 which is mostly in the central nervous system. It was introduced over twenty years ago and has been used to treat depression but without much success. Because it increases cAMP which is a universal intracellular messenger for many cellular activities, including growth and excitability, the drug has side effects when given in high doses. Several laboratories have given rolipram alone to rats after a spinal cord injury contusion and find that it does not, by itself improve function or regeneration (unpublished) and the rats do not tolerate high doses of the drug. This was the reason why Miami Project gave a low dose of rolipram to the rats and injred dibutyryl cAMP into the spinal cord. Note that nobody has yet replicated these results and we are trying to do so and also extend the results to chronic spinal cord injury.

    Rolipram is not currently approved by the FDA for any condition. Let me give you an idea of what it would take to get it into clinical trial. First, somebody must track down (and maybe have to buy) the original human safety data and present the data to the FDA in order to get the IND for clinical trial. Second, decisions will have to made concerning the route of administration of the drug in humans, particularly for regeneration. Should the drug be given intravenously, subcutaneously, orally, or even intrathecally? Third, once the route is chosen, the next decision is dose. Rolipram has significant side-effects. In humans, it produces significant nausea and vomitting. Rats do not tolerate long-term daily subcutaneous administration of over 3 mg/kg and the Miami Project gave 0.3 mg/kg. Whatever the choice, studies must be done to determine the pharmacokinetics of the drug in people with spinal cord injury, probably with CSF samples to determine how much of it gets into the spinal cord. Fourth, how long should the drug be given. In the Miami Project study, rolipram was started shortly after injury and continued for two weeks. The time scale of a rat and human are different (I estimate that one rat week is probably equivalent to one human month). Fifth, how late after injury should the treatment be started? Should rolipram be continued for 2 monnths? Fifth, how late should the treatment be started? Is it effective if started more than a month after injury, a year after injury, 10 years after injury?

    Nobody has injected dibutyryl cAMP into the spinal cord of a person, particularly after spinal crod injury. Please understand that it may create significant excitability of the spinal cord. Should the treatment be given intrathecally or intraspinally? What dose should be given. clinical study as well, to determine the best dose. What works for a rat may not be the same as a human. I want to emphasize that the safety parameters intrathecal db cAMP injections have not been established. What if the drug diffuses to the brain? Will it stop breathing, lower blood pressure, cause hallucinations, etc., etc.

    Cell transplantations. This is an often overlooked obstacle. In order to start activated macrophage transplants in the United States, Proneuron had to invest over a million dollars into each of its clinical trial centers, to establish a facility that fulfils GMP (Good Manufacturing Practice) and GCP (Good Clinical Practice) regulations, establish and guarantee quality control of the cells for transplantation. As such facilities are not available in all but a handful of centers, they have to be identified and site-visited. The NIH Stem Cell Resource Center, headed by Darwin Prockop in Tulane, has been working very hard over the past several years to establish bone marrow stem cells quality control. Let me assure you that has not been an easy job. They are still working on ways to make sure that batches of cells grown from bone marrow are similar. At Yale, they transplanted Schwann cells into two patients with multiple sclerosis and this was with the support of the Myelin Project and one of the best Schwann cell culturing laboratories in the country. What cells should be used? There is no agreement concerning the best cells to use.

    Cell transplantation is not yet a slam dunk and will require millions to implement. To my knowledge, for example, no center in Texas has experience with transplantation of cells into the spinal cord. You are probably asking yourself how this was done in Lisbon and Beijing. Well, in Lisbon, as you know, it took several years of work to develop the biopsy and transplantation procedure. It is probably the easiest of all the approaches, simply mincing nasal mucosa for transplantation. Is this the approach that should be used? In Beijing, they use cells cultured from aborted fetuses. It will be very difficult to identify a source of aborted fetuses in the United States. Most state has significant regulations that make use of fetal cells very difficult. For example, investigators are not allowed to contact or test the mothers for disease before abortion. The abortion procedure cannot be changed to accomodate sterile collection of the cells. Thus, fetal cells collected in the United States carry a higher risk of AIDS, hepatitis, and other diseases, as well as a risk of contamination.

    Decisions. Successful clinical trial design is all about making the right decisions. There is never sufficient data and one seldom has more than one or two chances to get it right.

    Wise.

  7. #67
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    Wise Young,
    the question is..... IS your group currently assessing rolipram plus db cAMP plus OEG transplants...

    thanks,
    Susan

  8. #68
    Susan, yes. We are doing the studies. I have posted this several times. Wise.

  9. #69
    Superstar,

    Contact information for Dr. Young is located on the main CareCure page. You can access it by clicking the CareCure Community link at the top of the page.

    By Superstar:
    Oh yeah, is there a reason i can not get an answer to this???

    Wise,

    Please help me understand which one of the two statements below is true. Honestly, i am trying to understand everything as quickly as possible and these two statements contradict one another. The reason i ask for an answer is because of the value it holds in terms of what's is going on in the quest for finding a cure using these specific drugs in combination with stem cells.
    thank you..
    Susan

    Ok, i have an important question. Wise, you wrote to me just the other day that and said "There is, to my knowledge, no experience giving rolipram in association with cell transplantation in chronic spinal cord injury (either in human or animals)."

    In the second paragraph of which Seneca posted that says "Wise Young wrote" says, My own group is currently assessing rolipram plus db cAMP plus OEG transplants... similar to the approach taken by Miami Project. We are also studying mechanisms of the early segmental recovery associated with OEG transplants into chronically injured rats, as well as spinal axonal myelination by OEG cells in chronically contused spinal cords.

    Superstar, Dr. Young has not contradicted himself. Here's what has been posted:

    According to you, Dr. Young said: "There is, to my knowledge, no experience giving rolipram in association with cell transplantation in chronic spinal cord injury (either in human or animals)."

    This is true. Rolipram has not been given in ASSOCIATION with cell transplants in CHRONIC animal or human subjects.

    The Miami Project used Rolipram with Schwann cell transplants and db Camp in ACUTE animal subjects.

    Dr. Young's lab is studying the use of Rolipram along with OEG transplants and db Camp in ACUTE animal subjects (as he says, similar to the approach taken by the MP).

    Dr. Young's lab is currently researching the mechanisms involved with recovery and remyelination using OEG ONLY (not in association with cell transplants) in CHRONIC animal models.

    So his original statement stands.

    I posted information regarding the research Dr. Young's lab is currently undertaking on page 2 of this thread.

    [This message was edited by seneca on 08-12-04 at 06:37 AM.]

  10. #70
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    Originally posted by Superstar:

    Wise,

    Being that i am a Director of Medical Research for a Humanitarian Endownment Company that has access to several million dollars for the sake of research, I offer you a proposal. Please contact me at your earliest convienience at http://www.sciwalker.com if you are interested in order for us to colloborate together in efforts in finding a cure.
    We will then be able to use your 25 plus years of knowledge in order to find the best treatment options available for sci using the money obtained through our Humanitarian Company.
    _Therefore, we will no longer need your bus, rather we have a hybrid that requires no gas!!!!! _
    Gods speed for a cure~
    Susan
    Superstar, I applaud your efforts to find a SCI cure for the community. I'm just concerned that the medical researchers at the Humanitarian Endowment Company might end up spending money and time reinventing the wheel. I urge you to consider convincing the Company to fund/donate their millions of dollars (several million or 300 million -- more the better) to Dr. Young's laboratory. I'm sure he would put it into his most promising research/clinical trial project. Of course, there are many other promising, current research projects enumerated on various threads in the Cure forum. These include those under the direction of Dr. McDonald, Dr. Peduzzi, and a host of others. You could pick anyone. Let us know what you decide.

    Thank you for working so hard to find a cure. Good luck to you.

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