Thread: ChinaSCINet Update

  1. #1611
    Quote Originally Posted by lunasicc42 View Post
    wise, based what you see concerning efficacy in these trials, are you guys still motivated to move this therapy to higher level chronics? And if so: whats the proposed timeframe? Has it changed or been altered?

    Because I would think that if this shows efficacy in the lower level injuries, the trial for higher injuries might be accelerated...

    And also when will you be able to comment surely on b/b/b?
    Lunasicc42,

    Yes, I am still motivated to move this therapy to higher levels. I don't know the specific time frame but it will depend on our ability to get permission to do the trials, to convince investigators to do so, and successfully raising the funds for the trials. Regarding the B/B/B, I don't know. We haven't analyzed all the data yet and I am not going to comment on the details of the data until it is published.

    Wise.
    Last edited by Wise Young; 02-08-2013 at 08:48 PM.

  2. #1612
    Quote Originally Posted by CAS View Post
    I know that I am likely to get a fall from this but as things seem to be progressing I cannot help but have a positive outlook the way developments have occurred during the last few years, in regards to potential cures and therapy’s etc.

    Dr Wise I know your going to start phase 3 soon. Could I ask as to when and for how long until the final phase (I assume) being four, will begin and end?. And how long will it take before the rest off us can participate in the treatment? If possible.

    Do you think that your therapy and others will be applicable to most of us by 2020? Or later like 2030.

    Thank-you for all your help
    CAS,

    Phase III trials lead to regulatory approval. Phase IV trials are post-approval, to look for long-term complications, etc. We are working as hard as we can to get the phase III started and completed before 2020. Barring any complications (such as lack of funding), we should know the whether the treatment is effective and safe in 2015.

    That phase II trials have yielded several surprising findings. The first is that MRI/DTI images are showing evidence fiber bundles growing across the injury site, suggesting of regeneration and that this grown is occurring a 6-12 months after transplantation of the cells. The second is that a majority of the transplanted subjects are showing improvements in locomotor scores without improvement in motor and sensory scores, at least at 6 months and in some cases at 12 months.

    We would like to confirm these findings as soon as possible in formal phase III randomized and controlled clinical trials. It is important to find out whether or not we see fiber bundles growing in the spinal cord when we do not transplant cells. Likewise, we need to find out whether the subjects do not show this kind of walking improvement without cell transplantation. Finally, of course, we are hoping that the subjects will show motor and sensory score improvements eventually.

    Wise.

  3. #1613
    Senior Member lunasicc42's Avatar
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    thanks for the response... and regarding my questioning regarding b/b/s is I know repetative but it's REALLY important
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  4. #1614
    Quote Originally Posted by Christopher Paddon View Post

    "At the risk of repeating myself, the fact that there is no change in motor and sensory scores does not mean that there has been no improvement in motor or sensory function."
    Especially the sensory part.
    I can kind of understand the motor improvement because of CPG. But how does this happen in sensory?

  5. #1615
    Quote Originally Posted by Christopher Paddon View Post

    I too am confused by the news that comes out of the ChinaSCINet. Here is a classic quote:

    "At the risk of repeating myself, the fact that there is no change in motor and sensory scores does not mean that there has been no improvement in motor or sensory function."
    What is so confusing with this quote? The Asia motor scores don't include all the muscles in the body. It only includes about 5 in the legs. Here is an example:
    if you can wiggle your big toe it will show on your motor scores.
    If you can wiggle your little toe it will not show on your motor scores, but you will have motor function.

    The quote makes perfect sense to me.
    Quote Originally Posted by paolocipolla View Post
    Moe,

    I... don't care about what I think ... you should just ignore my posts.

    I don't understand ... words.

    Paolo

  6. #1616
    Quote Originally Posted by Solan View Post
    What is so confusing with this quote? The Asia motor scores don't include all the muscles in the body. It only includes about 5 in the legs. Here is an example:
    if you can wiggle your big toe it will show on your motor scores.
    If you can wiggle your little toe it will not show on your motor scores, but you will have motor function.

    The quote makes perfect sense to me.
    Solan,

    Thanks for trying.

    Motor strength is graded on a scale of 0-5. When people cannot move a specified muscle on command at all, that is a score of 0. If they can move the muscle slightly against no resistance, so that it can be felt but not necessarily seen, that is a score of 1. If the movement can be seen, the score is 2. If the movement can oppose gravity, the score is 3. By the way, for the legs, that is quite a lot of strength, since the leg is heavy. If the movement can oppose manual resistance in addition to gravity, the score is 4. If the strength of the muscle is normal, the score is 5.

    In the case of the person in the video, that person is able to move his legs when walking but cannot move individual muscles when lying down. I have not checked for this specific subject but many of the subjects that are able to walk at KLS IV have 0 motor scores in their major leg muscles. For example, if the subject is lying on his back in a bed and we ask him to lift his leg from the hip, he cannot. If we push him to the left side, bend his right leg, and ask him to straighten his right leg, he is not able to do so. Or, if we ask him to flex his ankles up and down, he cannot. Or, if we ask him to wiggle his toes, he cannot. By the way, those are the five muscle groups that we test for the motor scores in the legs.

    We were surprised to find this. Of course, some subjects are able to move some muscles in their legs if they wiggle around and get spasms going. However, if we ask them to move specific muscles without any sensory activation, they cannot. We think that this is because they are activating the central pattern generator when they are walking. The central pattern generator is located in the lower spinal cord and contains programs for walking, trotting, running, etc. In order for the program to run, it must get sensory feedback from the legs. Note that sensory feedback is going to the CPG but not necessarily to the brain. Once the walking motion is started, the person can take step after step after step, each step activating the next step. They have to get it going and sensory feedback is needed.

    The concept that people with spinal cord injury walk with their CPG is not new. Many people who recover walking after spinal cord injury do not have strong voluntary control of their muscles. Nevertheless, they are able to walk and often for long distances with minimal help. Many people who are able walk do not have feelings in their feet or lower legs. By the way, I am presenting our observations and learning from them. I was not expecting this finding. Incidentally, the doctors at Kunming have been documenting the walking with electromyography as well. The subjects do show electromyographical activation of muscles when they are walking, so it is not just a trick that they are employing.

    I can understand that some people are confused but I am also puzzled by why the concept of activating CPG is so difficult for people to understand. After all, most people with spinal cord injury know what a spasm is. Spasms can be very strong. For example, leg spasms or multi-point movements that can be activated when people are being pushed in a wheelchair over cobblestone. Their legs often go rigid. Stepping motions can be activated by simply stimulating the L2 spinal cord. This has been shown many times now. I think that this is the beginning of walking. People are able to activate walking of their legs voluntarily even though they cannot move individual muscles.

    We want to document this unexpected phenomenon. We hypothesize that this occurs more frequently in subjects that we have transplanted umbilical cord blood mononuclear cells into but this hypothesis now needs to be confirmed in a phase III trial where we can compare transplanted subjects with non-transplanted subjects. We are also hopeful that we will eventually find some recovery of motor and sensory scores in the patients. We have not even collected 12 month followup data on many of the subjects. If the fiber bundles that we saw in the Hong Kong trial represent axonal growth, most of the subjects did not have growth across the injury side until 12 months. It is simply to early to conclude that the people will not get motor and sensory function. That is why we have asked the subjects whether or not we can follow them for another year.

    This is what doing Phase II trials are all about. We keep your eyes open and learn from what the subjects are doing.

    Wise.
    Last edited by Wise Young; 02-10-2013 at 09:27 AM.

  7. #1617
    Wise,

    I have a few questions for you.....

    1) When testing for voluntary motor scores in lying or sitting are you using the EMG? ie are we testing for the grade 1 scores? Or is the EMG only being used when stepping?

    2) Are you testing motor scores in the trunk at all? And if not, why?

    3) Will the goal of Phase III be to confirm the hypothesis that UBCB+Lithium+666 results in increased CPG-activated stepping if you observe no motor/sensory recovery by 12-18 month time points?

    4) If your observations are correct that bundles of axons have crossed the injury site but no motor/sensory recovery is observed (at say 18 months time points) would you consider returning to a chronic animal study to investigate why synapses are not being formed?

    Cheers
    Fly Pelican Fly

  8. #1618
    Quote Originally Posted by Fly_Pelican_Fly View Post
    Wise,

    I have a few questions for you.....

    1) When testing for voluntary motor scores in lying or sitting are you using the EMG? ie are we testing for the grade 1 scores? Or is the EMG only being used when stepping?

    2) Are you testing motor scores in the trunk at all? And if not, why?

    3) Will the goal of Phase III be to confirm the hypothesis that UBCB+Lithium+666 results in increased CPG-activated stepping if you observe no motor/sensory recovery by 12-18 month time points?

    4) If your observations are correct that bundles of axons have crossed the injury site but no motor/sensory recovery is observed (at say 18 months time points) would you consider returning to a chronic animal study to investigate why synapses are not being formed?

    Cheers
    Fly Pelican Fly
    1. In the trial, we are collecting the ASIA scores in the standard and recommended method. The patient is lying down and each muscle is tested in the prescribed position. The Kunming group has done EMG in walking patients but it is not routinely done. It is not part of our protocol.

    2. We are not testing trunk motor scores although we collect sensory scores. There is no validated clinical examination for trunk motor scores. There have been several efforts to develop an EMG form of such scores but these types of specialized tests would be expensive and difficult to implement in China.

    3. Good question. We are considering making the KLS and WISCI scores our primary outcome measure in the Phase III study. That will be discussed in our upcoming principal investigator meeting in Xi'an. I am not satisfied with either of these scoring approaches.

    4. Yes, of course, we are considering doing animal studies. Several laboratories have shown substantial regeneration and even reconnection of regenerating axons without locomotor recovery in animals. I am trying to put together a travelling clinical group to study these patients in the Phase III study, to study the mechanisms of walking in subjects who are walking without motor or sensory score improvements. I also want to emphasize that it is premature to speculate that these patients will not recover motor and sensory scores. We have not yet even collected all the 12-month data.

    Wise.
    Last edited by Wise Young; 02-10-2013 at 11:05 AM.

  9. #1619
    Quote Originally Posted by Wise Young View Post
    1. In the trial, we are collecting the ASIA scores in the standard and recommended method. The patient is lying down and each muscle is tested in the prescribed position. The Kunming group has done EMG in walking patients but it is not routinely done. It is not part of our protocol.

    2. We are not testing trunk motor scores although we collect sensory scores. There is no validated clinical examination for trunk motor scores. There have been several efforts to develop an EMG form of such scores but these types of specialized tests would be expensive and difficult to implement in China.

    3. Good question. We are considering making the KLS and WISCI scores our primary outcome measure in the Phase III study. That will be discussed in our upcoming principal investigator meeting in Xi'an. I am not satisfied with either of these scoring approaches.

    4. Yes, of course, we are considering doing animal studies. Several laboratories have shown substantial regeneration and even reconnection of regenerating axons without locomotor recovery in animals. I am trying to put together a travelling clinical group to study these patients in the Phase III study, to study the mechanisms of walking in subjects who are walking without motor or sensory score improvements. I also want to emphasize that it is premature to speculate that these patients will not recover motor and sensory scores. We have not yet even collected all the 12-month data.

    Wise.
    Thanks Wise.

  10. #1620
    Dr.Young ,
    Hi, Did any of china sci network centers use FES after their umbilical cord blood cells transplants on subjects? If not, do you think using FES on some specific muscles after transplants (in addition to walking program) could have some effect on motor scores etc. ? just a thought .

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