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Thread: Regeneration vs Cell Replacement Therapies

  1. #31
    Dr. Young, have OEGs been shown to secrete NT-3 or NGF? I saw that they secrete GDNF and possibly BDNF, and maybe express the L1 CAM [can't remember for sure], but don't know about NT-3 and NGF.

    -Steven
    ...child, when life don't seem worth livin', come to jesus and let him hold you in his arms

  2. #32
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    Wise,

    Just out of curiosity, what are you currently doing in your labratory? It seems that you must understand the drugs after this amount of research that you have invested your time in. I am not trying to say, you must know.. Only that i hope to God you do! Do you know what the cells do and if so why are you not using them to free us from paralysis???? Is there some reason that you are waiting to combine these cells with the drugs of which you speak about? Please, please help us if you can..

    The time has come for a cure!!

    Gods speed to our freedom~
    Susan

    Gods speed to you~
    Susan

  3. #33
    Hi Superstar, here's the latest update from Dr. Young's lab posted in June:

    By Dr. Young:
    Briefly, our Center has four principal investigators: Marty Grumet, Ron Hart, Dongming Sun, and myself. We have a large number of related spinal cord injury projects, some of which are shared and others are primarily run by one investigator. Many of the studies are in progress and therefore I don't know the results.

    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. Crista Adamson in my group is studying erythropoietin effects on spinal cords. She is winding up studies on therapeutic vaccine, looking at the antibodies that are being generated when rats are vaccinated with spinal cord and liver homogenates. I have a student working on how axons make branching and pruning decisions when they grow in culture. I have one postdoctoral fellow winding up a study on stem cell transplantation into atrophic muscles.

    I am working closely with Dongming Sun on studies of umbilical cord blood stem cells (human and rats). So far, we are beginning to have some success growing out these cells and transplanting them into the spinal cord. Dongming is also winding up studies of macrophage transplants to treat acute spinal cord injury (a la Proneuron & Michal Schwartz).

    Marty Grumet and his colleagues in the laboratory are studying combinations of neural stem cell transplants and the cell adhesion molecule L1, finding that the combination is better than either alone. Marty and I are collaborating on projects looking at chondroitinase and combinations of that with various cell transplants. He has a number of other people in his group studying neural stem cells.

    Ron Hart does gene expression studies on the spinal cord. He is studying inflammatory responses and the effects of various anti-inflammatory drugs, identifying regenerative and neuroprotective genes in the spinal cord, assessing a number of acute spinal cord injury therapies including COX-2 inhibitors and nicotine. Because most of our projects involve gene expression, he is a collaborator on almost all the studies in the Center. In addition, he has extensive collaborative studies going on with several dozen labs at Rutgers and other institutions.

    Wise.
    source

  4. #34
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    Dr. Wise

    With all the due respect I gotta say what strikes me as a respond to your explaination.

    #1; You say dont know what'll work best from the combo therapies, well nobody knows thats y is still called a 'trial'.
    That's the only way to find out especialy when the patients are willing to give it a try.

    #2;You say that it doesn't matter much what Wise says; it matters what the clinicians believe is a better combination, true but i think their first choice to get an opinion from, won't be the paralysed people but researchers like you, (who have lot more experience than the clinician themself).

    P.S. I don't mean to put any pressure on you but, I & many peeps here strongly believe that you are one of best hopes in this comunity, & the right man to pull this through.

    Luigi.



    Originally posted by Wise Young:

    luigi, scott, susan,

    Thanks, but let me try to explain again. I don't know what combination therapy will work best in humans. There are pros and cons to each of the combination therapies. While I greatly appreciate your confidence in me, it is not appropriate for me to endorse a particular combination over another.

    Three combination therapies have now been reported to be effective in animal studies.
    • Schwann cells plus rolipram plus db cAMP (Miami)
    • Bone marrow stem cells plus rolipram plus cAMP (UCSD)
    • Schwann cells plus GDNF plus chondroitinase (Louisville)

    Others that will be reported this fall include:
    • Radial glial cells (neural stem cells) plus L1 (Rutgers)
    • OEG cells plus rolipram plus db cAMP (Rutgers)

    There are likely to be other combinations:
    • OEG cells plus chondroitinase
    • Neural stem cells plus Nogo inhibitors

    Combination therapies are the most difficult treatments to test in clinical trial. The safety and feasibility of the individual therapies need to be established first. For example, relatively few centers are currently equipped to carry out cell transplants and so that must be a first priority since all the combination therapies involve some kind of cell transplant.

    A source must be found for each of the components of the combinations. For example, the question is where one would get Schwann cells, olfactory ensheathing glia, or neural stem cells. Considerable effort must be expended to get the drugs involved. For example, rolipram is currently not being manufactured by any pharmaceutical manufacturer and it has significant side effects in people. It is only available in small quantities, to my knowledge, for animal studies. So, a manufacturer has to be identified. If a drug is made by a company, we would have to convince the company to allow the drug to be used in clinical trial. For example, GDNF is made by Amgen, chondroitinase by Seikagaku, Nogo blockers by Novartis and Biogen, etc., etc.

    A clinical trial design must be established. What will we use as the control? The problem is that nobody will want to be randomized. So, I think that the design should be a comparison of two treatments. The approach therefore should be to identify two combinations and see which one is better. Of course, the two combinations should be potentially equally effective.

    In summary, the choice of the drug combinations must be based on practical considerations, such as what cells are available and acceptable... the combinations will depend on what drugs are available and are the safest. Finally, the clinicians must be convinced to carry out the trial. It is not what Wise Young says that is important but what the clinicians believe is the best combination that they are willing to try.

    I hope that this helps.

    Wise.
    every time you fall,
    stand up tall....
    come back for more

    [This message was edited by luigi91377 on 08-07-04 at 12:51 AM.]

  5. #35
    In fact, I expect that we might be able to raise funds for only a single multicenter trial for chronic spinal cord injury research in the U.S. during the coming year. The choice of the therapy and the clinical trial design therefore must be carefully chosen.
    Dr. Young, other clinical trials *must* be done in other countries like Europe, Canada, Australia, UK or else... What do you think about making a Top 5 of the combo therapies you believe are the best?... You adjust the Top 5 as scientific news are coming... Raising money will be easier if we have fixed targets with good pdf abstracts docs showing this is not bull shit?...
    George

  6. #36
    Senior Member mk99's Avatar
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    "For example, rolipram is currently not being manufactured by any pharmaceutical manufacturer and it has significant side effects in people. It is only available in small quantities, to my knowledge, for animal studies"

    What about the completed phase2 Rolipram trial for MS that was sponsored by NINDS? Where did they get the human Rolipram from?

    "Treatment (8 months) - Patients will take Rolipram tablets in increasing doses every 2 to 3 days for the first month of this phase until their individual maximum tolerated dose is established. Dosing will continue at that level for the rest of the treatment phase."

    Study Here

  7. #37
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    Seneca,

    First off, thank you very much for your reponse to my question regarding what's up with Wise's lab..

    Ok, i have an important question. You say that Wise wrote this, well Wise told me just the other day that "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, it says, "My own group is currently assessing rolipram plus db cAMP plus OEG transplants... similar to the approach taken by Miami Project."

    Please tell me that there is some explanation for the discrepancy of which i am reading.. I have thought about this for a while and see no logic in any of this.. very bad feeling..
    Dr. Young, you have over 25 years of knowledge beneath your belt in the mystery of sci..
    We need you to be honest with us, please i am begging you to make me understand why such contradictions have been posted.. I am very sad and truly hope you must have made a mistake... We are putting together a large research and rehabilitation center both in the US and outside and i need your trust so that A Cure Will be Found very soon!
    thank you,
    Gods speed~
    Susan

  8. #38
    Senior Member mk99's Avatar
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    Susan,

    I think this means that Miami Project was doing acute injuries with the Schwann cells, db cAMP and Rolipram combo therapy.

    Dr. Young's lab (among others I'm sure) is doing the same combo therapy in a chronic injury model.

    I know there are labs watching this work on chronics with great interest.

    Therefore no bad feelings from you are needed.

    [This message was edited by mk99 on 08-07-04 at 09:20 PM.]

  9. #39
    I love Superstar's enthusiasm!!

  10. #40
    I appreciate your impatience but I have given you all the evidence that I know. There is simply not enough evidence right now to predict which combination therapy will be successful in clinical trial or even in chronic spinal cord injury. The animal experiments are being done right now and nobody knows what the results will be. There are too many unknowns to predict the results. Clinical trials must be evidence-based. Too much is at stake here to base the next clinical trial on speculative guesses.

    Perhaps an analogy will help. Suppose that a sugar daddy gives us $300 million for spinal cord injury research and says to us, go invest the money for the cure. Let's take some of the zeros from the sum so that it is more easily graspable. So, suppose that we have $300 in our pocket. We need to invest it to make $10,000 (a cure) quickly. Where would you invest it? Would you go to Las Vegas and bet all the money on one poker game? I hope not. The odds of winning are low. Let us play to win. I think that we must invest in activity that is more likely to yield a return. We must spread our bets or preferably not gamble at all. Research (knowledge) improves the chances of winning.

    If you ask me what therapy you should try as an individual, I would give a different answer than if you asked me what therapy the country or world should be investing their very limited resources on. If you ask me what you should choose as an individual, I would say that OEG treatments in Beijing now offers the best benefit:risk ratio. The benefits are modest and the risks are reasonably low. I would also say that your chances of getting more recovery will be higher if you wait until we know more about combination therapies. Finally, I believe that clinical trials will start in the United States.

    Wise.

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