Thread: ChinaSCINet Update

  1. #1221
    Senior Member
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    Wise,
    Correct me if I'm wrong;but do the studies you're doing now use umbilical cord blood stem cells as opposed to embryonic stem cells? I watched a video where you discussed doing research in Texas using umbilical cord blood stem cells. Are there disadvantages to not using embryonic stem cells in research?
    If you had a crystal ball how far away would you say we are from a "cure"?
    Thanks,
    Kyle
    C4/5 incomplete, 17 years since injury

    "The trick is in what one emphasizes. We either make ourselves miserable, or we make ourselves happy. The amount of work is the same.” - Carlos Castaneda

    "We live not alone but chained to a creature of a different kingdom: our body." - Marcel Proust

  2. #1222
    Originally Posted by Wise Young
    I don't think that B & B requires recovery of voluntary movement.

    Quote Originally Posted by lynnifer View Post
    What do you mean 'doesn't require recovery of voluntary movement?'
    I guess he was just kidding me

    Paolo
    In God we trust; all others bring data. - Edwards Deming

  3. #1223
    Quote Originally Posted by paolocipolla View Post
    Originally Posted by Wise Young
    I don't think that B & B requires recovery of voluntary movement.



    I guess he was just kidding me

    Paolo
    Paolo,

    I was not kidding you. When I refer to voluntary control, I mean direct excitatory and inhibitory control of muscles, such as the ones that operate your major joints and those that connect to your spine, ribs for postural control, tongue, larynx, etc. However, we have many muscles that we have limited or minor indirect voluntary control of. Bowel and bladder are amongst these. Others include the heart, stomach, vascular sphincters, pupillary contraction. Yes, you can contract your anal sphincter but it is not a muscle that you can easily open and close at will. Likewise, most people cannot open or close their bladder sphincter voluntarily (at least I can't). We can inhibit these reflexes to some extent but anybody who has experienced a full bladder knows that we can't inhibit these reflexes for long. Likewise, we can initiate the defecation and micturition reflexes but we have limited or no voluntary control over these reflexes once they are initiated. They are operated by spinal cord centers.

    After spinal cord injury, most people retain their defecation and micturition reflexes, as long as the lumbosacral spinal cord where the control centers are located is uninjured. These reflexes are activated when there are feces in the anal canal or urine in the bladder. These centers may become hyperexcitable, a form of spasticity. So, the bladder may release its urine when relatively little urine fills it or a small amount of feces enters the anal canal. You can inhibit these reflexes with drugs. For people who have had sacral injuries, these reflexes may be lost. In such cases, there is fecal incontinence (i.e. the sphincter does not close) or the bladder becomes flaccid. Sometimes, the sphincters still maintain tone and remain contracted but can be manipulated to relax.

    The ASIA motor score reflects 10 major muscles in the arms and legs. Each of these muscles control one of the large joints of the limbs, i.e. in the legs, they include the hip flexors (psoas), knee extensors (quadriceps), ankle flexion (anterior tibialis), ankle extensors (gastrocnemius), and the big toe extensors (extensor hallucis longus). The ASIA motor scores are sums of the scores of the voluntary strength of these muscles, tested manually. For example, 0 indicates no voluntary movement, 1 is trace movement that can be palpated, 2 is full or partial range of movement with gravity eliminated, 3 is full range of movement against gravity, 4 is movement against moderate or strong resistance, and 5 is normal strength.

    When I said that there were no changes in the motor scores of people, I was referring to the muscles tested according to the ASIA exam. Subjects are showing locomotor improvement without changes in their motor score in our study. My answer to your question assumed that you were referring to the motor score, which reflects voluntary control of the muscles tested. In any case, we have mostly indirect and limited control of our bladder and bowels and recovery of these functions is not necessarily associated with voluntary control of other muscles, particularly those that are tested in the ASIA motor score.

    Wise.
    Last edited by Wise Young; 11-15-2012 at 12:59 PM. Reason: typographical and grammatical errors

  4. #1224
    Senior Member lynnifer's Avatar
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    Clearly understood. Be nice to get both back tomorrow. lol
    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

  5. #1225
    Quote Originally Posted by KyleP2112 View Post
    Wise,
    Correct me if I'm wrong;but do the studies you're doing now use umbilical cord blood stem cells as opposed to embryonic stem cells? I watched a video where you discussed doing research in Texas using umbilical cord blood stem cells. Are there disadvantages to not using embryonic stem cells in research?
    If you had a crystal ball how far away would you say we are from a "cure"?
    Thanks,
    Kyle
    Kyle,

    There are many advantages to umbilical cord blood cells and many disadvantages to using embryonic stem cells. Incidentally, I refer only to clinical advantages and disadvantages, not political or social ones.

    Let me first talk about advantages of umbilical cord blood cells. They are obtained from the umbilical cord, representing the residual blood left in the placenta after the baby is born and the umbilical cord has been clamped. Umbilical cord blood contains many stem cells, more than bone marrow, for example. Umbilical cord blood has also been safely used to treat thousands of people, probably over 100,000 people since the early 1990's. There is no evidence that they produce tumors. They are collected by public umbilical cord blood banks that store them in large numbers (over 200,000 units around the world) so that the units can be matched by HLA antigens (these are the same antigens that are used to find organ donations). We used HLA-matched umbilical cord blood cells donated by Stemcyte, the largest and most accredited commercial cord blood bank in the world.

    We considered embryonic stem cells but rejected them for our first clinical trial for the following reasons.
    1. Embryonic stem cells are usually obtained from a cell line that have been grown from a single embryo. In other words, they are very unlikely to be matched to individual that is receiving the cells. From that perspective, the cells are likely to be rejected by the immune system of the host. When Geron did its trial, it was assuming that the cells would not be immune-rejected if they give a period of immune-suppression (such as cyclosporin). That is an untested assumption.
    2. Embryonic stem cells tend to grow into stem cell tumors called teratomas. In animal studies, embryonic stem cells transplanted into the spinal cord will either be rejected (usually at 2-3 weeks) or will grow into a tumor called a teratoma. This is not so surprising because embryonic stem cells evolved to generate babies. When enough embryonic stem cells are placed together in one place, they will produce cells of many different types. That was the reason why Geron went to so much trouble to differentiate the cells to the point where they are no longer stem cells before transplantation.
    3. Relatively few embryonic lines have been produced since 1997. Even the best laboratories growing embryonic stem cells from blastocysts usually were able to get one embryonic stem cell line for every 20 or so blastocysts. The embryonic stem cell lines that are grown vary a great deal. Some are more pluripotent than others. Due to limitations on embryonic stem cell research, there has not been enough embryonic stem cell lines (only a few hundred) produced and compared to find the best ones for different diseases and conditions.
    4. Many of the embryonic stem cell lines that have been tested extensively enough to be used clinically are very old. For example, the H1 line from which Geron derived the oligodendroglial precursor line used for clinical trial, was amongst the first embryonic stem cell line produced in Wisconsin, more than 15 years ago. It has known chromosomal dropouts and other genetic abnormalities.


    I sincerely wish that I have a crystal ball. All that I know is that if we don't do clinical trials, we won't get there. We do the trials and we test the best therapies that are available. If that therapy works, we either add to it or compare it against other potentially better therapies, and so on. Eventually, we will reach the cure. For the first clinical trial, I believed that we should test the safest and most promising cell transplant, combined with a safe drug. Both umbilical cord blood mononuclear cells and lithium have been reported by many laboratories to improve function in animals with spinal cord injury. If it works, that would be great. If not, we go on and test other therapies.

    Wise.
    Last edited by Wise Young; 11-15-2012 at 01:04 PM.

  6. #1226
    Quote Originally Posted by lynnifer View Post
    Clearly understood. Be nice to get both back tomorrow. lol
    Yes, I would dearly love to see that as well. Micturition and defecation is like locomotion in that it is programmed into the spinal cord. I believe that relatively few axons may be necessary and sufficient to restore both functions. We are monitoring these functions in our trials (through the SCIM test which asks patients about the bowel and bladder function). If our phase 2 trials show that there is bowel and bladder recovery, we would of course introduce more stringent tests of such function beyond just a questionnaire. We should remember that bowel and bladder is at the bottom of the spinal cord. They are likely to be amongst the later functions to reappear from regenerating spinal tracts.

    Wise.

  7. #1227
    Quote Originally Posted by kivi66 View Post
    "The data indicate that the procedure is safe and we are seeing some regeneration and recovery"(#1208)
    Dr.Wise, are you sure that you don't confuse the term "regeneration" with the term "plasticity"?
    kivi66, you are right. In my mind, when I see these long tracts growing up and down the spinal cord, I am thinking regeneration. However, until they reconnect with neurons, we should not call these regeneration.

    We have to determine whether they are reconnecting and therefore I have been in discussion with other scientists to figure out electrophysiological methods of demonstration reconnection. Of course, if we find that those patients who have these long regrowing tracts show recovery and patients that do not show such regrowing tracts do not show recovery, then we would be justified to say that the tracts have regenerated. It is still too early to say regeneration and I should have used the word "regrow".

    Wise.

  8. #1228
    Quote Originally Posted by Tachtig View Post
    Thank you Dr Young for your detailled answer. I was not jumping to any conclusion or saying UCBMC doesn't work at all, that's why I said I would wait for the upcoming results / report. What I was asking for is if we could expect a conclusion about the use of UCBMC besides that if it is safe to use or not.

    I was asking this question because this is the phase 2 trial and phase 3 is being planned and I read this.



    Here it says that in phase II the effect of the drug will be tested. That's why I thought we might get some light on this matter in the upcoming results. But as I understand correctly this will take a while before the final phase II results will be available?

    Whatever the result will be I totally agree that you have created an amazing network for human trials and I'm looking forward to whatever this may bring in the future.
    Tachtig, I was not referring to you when I said that some are jumping to conclusions. Many are professing to be disappointed by the results. One person actually predicted that this means that the trial has failed. Another person said, based on one case of a person with apparent white matter regrowth but not correlating with motor or sensory scores, that the data "does not look very promising". Of course, they are entitled to their opinion but I think that their judgment is premature for the following reasons.

    The Hong Kong trial involved only 8 subjects, using only the two lowest dose of the umbilical cord blood and did not include lithium. Yes, some of the patients are 1.5 years after transplantation. But, it may take longer than 1.5 years for spinal tracts to reconnect. We are asking and hoping that the subjects will return for 2 year followup exams. If possible, we hope to test them further with motor evoked potentials, to see if they can indirectly activate motor responses in their legs, even though they may not have consistent voluntary activation.

    The Kunming trial has 20 subjects and includes all five treatments groups, including the highest dose of umbilical cord blood cells and lithium. We will have the 6-month followup data by the end of November (hopefully). In kunming, they are sending teams of nurses to the subjects' homes to do the examinations. To date, as I have mentioned, we have seen some recovery of locomotor function in patients even as early as 6 weeks.

    There is a huge amount of work that needs to be done before we can start the phase III trials. In the next six months, we have to get all this data analyzed and published. For example, we have to establish a GMP cell processing facility in China. We will need to get IND applications approved in China, U.S., Norway, and India. If we don't start this work now, we won't be able to initiate the phase III trial until 2014. In my opinion, the data that we have obtained to date suggests that it is worthwhile going to phase III trial. Of course, the data that we are collecting in the Kunming trial may alter that opinion.

    Wise.

  9. #1229
    Paolo,

    I'm a member of the spinal cord injury community with an injury very similar to yours, and have become increasingly frustrated with your posts every day. I mean come on, what are you really trying to do here, discredit the very thing that could make us better? Make us lose hope? Even worse, make the doctors/scientist who are trying so hard feel like we' re an ungrateful lot? I mean really, I just can't take it anymore, enough is enough!

    Why don't you try doing something productive instead of taking potshots at every little thing Dr. Young has to say. With the time/energy you spend here every day I'm sure you could do all sorts of great things raising money and awareness for a cure.

    -Mike
    Last edited by Chassmain; 11-15-2012 at 05:11 PM.
    I am the Quad in Quadomated. Come read about Life and Technology through the Eyes of a Quad
    http://www.Quadomated.com/

  10. #1230
    Dr. Young,

    I want to thank you for all your hardwork, dedication, and tireless efforts to find a way to someday make us even a little bit better. I admire your commitment, openness, and compassion and hope that someday we can walk side-by-side down the street. You and those who work beside you give me hope every day.

    I thank you for that!
    -Mike
    I am the Quad in Quadomated. Come read about Life and Technology through the Eyes of a Quad
    http://www.Quadomated.com/

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