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Thread: Wise - Is there any hope of returning B/B/S to T12-L1SCI's?

  1. #1
    Senior Member Kaprikorn1's Avatar
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    Wise - Is there any hope of returning B/B/S to T12-L1SCI's?

    Huang's OEG, Pedruzzi's ASC, Lima's, etc. treatments have all shown minimal improvement(1-2 levels) in motor function and better improvement(3-4 levels) in sensation but all required much PT after surgery to obtain these gains. Even the latest combo results of Pedruzzi, Lima, et.al. were only showing 10% better results according to EAA's post on their latest studies.

    Even if a T12 or L1 were to recover down to S2, without PT, the previously touted results would not occur. Since you can't exercize BBS muscles to increase their motor activity, a T12 or L1 would be pretty much out of luck when it comes to restoration of function.

    My question is are we really SOL at this time and if so, are there any animal trials that indicate ESC will restore BBS to us "cord-bottom" cripples?

    Kap

    accept no substitutes

  2. #2
    Kap,

    • The sensory recovery, if it occurs, is quite rapid and does not appear to require much physical therapy.
    • Published animal studies suggest that cell transplants alone produce definite but modest gains by themselves and that combination treatments have better results. While it is interesting what EAA says, you should not be making any decisions or coming to conclusion based on anecdotal third-hand reports. I have been burned on so many occasions, jumping to some conclusion about a study only to find that the published or first-hand report is very different or studies are not replicatable.
    • Given the fact that combination therapies have not yet been tried in humans, I don't understand why you would be jumping to the conclusion that combination therapies would not have any effects on lower thoracic injury.
    • The MASCIS model of spinal cord contusion (that we developed and is now the standard model of rat spinal cord injury) is directed at T13 (just above the L1 spinal cord at vertebral level T9-10). It is equivalent to a person who has a T9 injury. When researchers say that a treatment improves walking in that model, it means that the treatment is beneficial for a lower thoracic spinal cord injury.
    • Doug Kerr at Johns Hopkins and also the Wisconsin group have now shown that mouse and human embryonic stem cells (respectively) will replace neurons and motoneurons in the lower spinal cord. In the case of Doug Kerr, he showed that the mouse embryonic stem cells not only replace motoneurons but the new motoneurons sent out axons into the spinal roots and probably account for 10% of the innervation of muscles in the animals. This is very exciting indeed. Because of politics, we have had a four year delay in availability of human embryonic stem cells for human use. Hopefully this will change this month when Congress votes on the stem cell bill and allows NIH to fund research on human embryonic stem cells that are being discarded from fertility clinics. This is of course assuming tha President Bush does not veto it.

    Here are some points that you can make to your Representative and Senators.

    1. Embryonic stem cells are the only cells that have been shown to produce functioning motoneurons when transplanted into the spinal cord. For people like yourself and Sherman Brayton, stem cells will be important.

    3. Time is of the essence. For the tens of thousands of people who have motoneuronal disease, this is a life or death issue. The 5-year survival rate after a diagnosis of amyotrophic lateral sclerosis is less than 10%. People are dying. We already have had an unnecessary four-year delay of embryonic stem cell research. Every month we delay means probably thousands that will have died unnecessarily.

    4. The current federal policy has severely curtailed embryonic stem cell research in the United States. There are only 22 NIH-approved human embryonic stem cell lines and all of these have been contaminated by mouse feeder cells and exposure of bovine serum.

    5. Adult and umbilical cord blood stem cell research is being underfunded as well. Although many scientists believe that adult and umbilical cord blood stem cells may one day be useful for treating people, federal funding of all human stem cell research has been limited to less than $250 million in 2004.

    6. The United States is falling behind in stem cell research. Less than 1% of the NIH budget being spent on what most scientists believe will cure many of our most terrible diseases. Please note that England and even Singapore spent more money on stem cell research than the United States.

    7. Our priorities are wrong. Please contrast the paltry stem cell research investment to over $5 billion that the United States spent on smallpox and anthrax vaccines. Not only are both of these low probability bioweapons but it is easy for any rogue country or terrorist organizations who have to capability to produce viruses to modify the viruses so that the vaccines are ineffective.

    Wise.

  3. #3
    Senior Member Kaprikorn1's Avatar
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    Wise...

    Assuming that Kerr's results would translate into similar quantitative improvement in humans, and new motoneurons would grow enough axons to enervate the hip, leg, etc. for walking, would this amount of axonal regeneration also represent sufficient enervation to restore BBS in T12/L1 contusion injuries?

    If the answer above is affirmative, and new "clean" lines of ESC were available, can you give ANY estimate on the timeline for an effective therapy to be available?

    As you know, I'm a walking L1 para with NO BBS, and at almost 54 years of age, often wonder if I'll be cathing, dig stimming, etc. at age 70, assuming I live that long.

    Kap

    accept no substitutes

  4. #4
    kap,

    While I am willing to predict based on science, one thing that I cannot predict is politics and economics, both of which will affect the progress and time it will take for stem cell therapies to come into use. In 2000, I would not have predicted that in 2005 there is still no place in the world that has tried transplanting human embryonic stem cells. This is not because of the science but because of politics. Because of the slow-down in human embryonic stem cell research, both umbilical cord blood and bone marrow stem cell work is beginning to catch up. In the coming four years, assuming no change in the Administration policy, probably adult stem cell research will pull ahead of embryonic stem cells.

    When the cells become available, there are several problems that must be solved before human embryonic stem cells can be used to treat human spinal cord injury.

    1. Immunocompatibility. We have only two choices for immunocompatible cells. One is using HLA-antigen matched cells. To do this, we must have several thousand human embryonic stem cell lines. The other is to use cloned stem cells. Cloning is still very inefficient right now. To date, only one cloned human embryonic stem cell lines has ever been produced (in Korea).

    2. Reducing probability of stem cell tumors. There are currently three ways of doing this right now. The first is to avoid growing the cells for long periods of time in culture. These are called early-passage cells. The second is to pre-differentiate the cells with retinoic acid and then with sonic hedgehog. The third is to screen the cells for the presence of aneuploidy or any chromosomal abnormalities that may indicate the tendency for cancer formation. I believe that more efficient and sensitive assays are necessary.

    3. Establishing safety and efficacy. Testing the cells in human spinal cord injury. In the United States, Phase 1 trials may take 2 years, assuming that the trials indicate no problem. Phase 2 trials to optimize the therapy (dose and injection site) may take 2-3 years. Phase 3 trials to establish efficacy may take 3-4 years. So, in total, it may take 7-9 years. But, all of the above assume that the cells are available for clinical trial.

    However, several factors may help push this along. First, because ALS is such an urgent condition with desperate time lines, it is possible that the FDA may allow phase 1 and 2 trials earlier on a compassionate use basis. Second, progress overseas may push the time lines as well. The country that develops several thousand human embryonic stem cell lines, for example, will dominate the field. I think that there are organizations in Singapore, England, China, and Korea who want to achieve this. Third, I am hoping that the China SCINet may push progress along.

    So, it is very hard to predict. It upsets me that we have lost 4 years already and the upcoming 4 years don't look like as if they will be very different.

    Wise.

  5. #5
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    T12 and below- are e stem cells the only real option for us? Can nothing else create motoneurons to re-activate the local pattern generator? What about adult stem cells? Nasal cells? How would cellular activity work to restore bowel, bladder, and sexual function? Or is it time to buy a noose, and get it ready for a hangin'?

    sherman brayton

  6. #6
    Sherman, I think that adult stem cells will eventually be able to do it. However, so far, we don't know how to make them do it. Don't buy a noose yet. Wise.

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    I guess the status quo has no problem watching people with ALS continue to die without hope. I fail to see why shortcuts would be reckless to a condition that is so virtually beyond hopeless.

    sherman brayton

  8. #8
    Junior Member gemz's Avatar
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    What about a T12 complete who has some lower motor neurons remaining? would they only benefit from ESC too?

    gemz

  9. #9
    gemz, I hope so. Wise.

  10. #10
    Sherman, More risky therapies have been applied to conditions where death is imminent. I was simply pointing that out as one of the reasons why embryonic stem cells may go to trial earlier than expected. I know that investigators have already proposed clinical trials of embryonic stem cells to people with progressive motoneuronal disease. Wise.

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