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Thread: Wise Live at Working 2 Walk!

  1. #1
    Senior Member kate's Avatar
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    Wise Live at Working 2 Walk!

    Donna starts by asking if anybody in the room does not know Wise Young? No hands go up.

    She talks about how important CareCure has been to all of us, and Wise's tireless advocacy and availability to people in chairs.

    Wise takes the stage.

    Thanks for this great meeting; organizers, you've hit another home run.

    I've been asked to give a 101 on spinal cord injury. After yesterday's meeting I added a few slides. I'm going to talk about the barriers that this thing should address. I hope by the end of this, you'll feel as I do that this is not a never-never land. It's something we can conquer.

    I want to bring up a couple of points. One is how tired I am of opening a newspaper and reading that someone will never walk again.

    In the USA there are over a million spine injuries per year, but only 10% of them get a spinal cord injury, because we have this amazing protective system called the vertebrae. it only weighs a few pounds, which is astounding. It's been said that all of us will have back pain sooner or later . . . the pain we feel is meant to keep us from stressing that vertebrae system.

    What's contusion? What's compression?
    The great majority of sci's are caused by bone pressing into the cord. Contusion is when the bone presses rapidly into the cord . . .compression is when the bone presses slowly into the cord, cutting off the blood supply. The cord is more resilient than the brain. You can press on it for 20 minutes and it will still be okay; the brain gets damaged after 6.

    Most injuries involve both. Early decompression after sci is critical; as recently as the 1980's neurosurgeons were saying there was no need to remove bone from damaged cords. That's how deep was the conviction that a damaged cord was not worth anything.

    The cord is protected by the this membrane called the dura mater (tough mother); it floats in cerbrospinal fluid. The dura's job is to redistribute compressive forces; it's so tough that even with a very sharp knife you can barely cut through it.

    The cord is stretchable -- it can be stretched by as much as 50% as long as you do it slowly. What's the speed at which axons break? half a meter per second.

    Andy Blight did a study in the 80's that will never be replicated . . . contused the cords of cats and then went and counted the axons. What he found is that the myelinated axons were the weakest, because the little spaces between the bits of myelin wrapping are like weak spots in a chain of links.

    Contusion damages large myelinated axons, and compression injury damages small unmyelinated axons.

    Perfectly understandable image up of what a laminectomy does -- remove the bone that's near the cord. Showing sections of rat cords with injuries caused by dropping 10 grams onto them.

    Secondary injury -- which people in the field did not even believe in 30 years ago -- is caused by calcium into neurons. Calcium rushes into injured neurons, and if the level of it is high enough, it will activate enzymes that kill the cell. At low levels calcium is just doing a job; at high levels it's toxic.

    Methylprednisolone (think sylvester stillone for pronunciation) ... Wise gave a huge dose of the drug to patients -- a thousand times higher than was ever given before -- this was in 1981, and he says that if he asked permission from the FDA to do this today it would probably be denied. He couldn't sleep the night this was done, because many of his colleagues warned that he was going to kill these patients with such a high dose.

    Okay, so should we really hate the secondary injury? Not exactly; it's there for a reason, and it's actually involved in tissue repair. Within 5 seconds after you contuse the cord, there are cytokines on the scene, and they're producing growth factors and calling for macrophages that remove toxins and myelin fragments that inhibit growth.

    Talking about a colleague who uses staining to show that the cells that go to the injury site are coming from the bone marrow . . . their job is to rebuild blood vessels. There are also astrocytes that restore the blood brain barrier, which is a sort of field that protects our central nervous system. If you have a leaky blood brain barrier, you're one of the people who responds badly to certain Chinese food with a lot of glutamate.

    Okay, what about the glial "scar" ? Astrocytes line the boundaries between the cns and the pns. These cells look at severely injured tissue and see it as foreign, meaning they see it as "outside" the central nervous system. Every week, he says, somebody on CC gets on to ask if they should have a surgeon cut out their scar . . . and every week he answers the same thing: you will get a worse scar if you do, because it's not really a physical scar. The act of "cutting" would introduce more astrocytes . . .

    Image of chronic sci -- in this case a rat with an 18 week old injury. There are macrophages sitting right on the surviving part of the cord, eating up cells.

    What about regrowth? Lots of vertebrates do have the ability to regrow their cords, like lamprey, zebrafish, tadpoles, newts, lizards . . . they're all short, less than 2 cm in diameter. Until around the time of world war II, people died from sci, so there was no time for evolution to work out a way to regrow human cords.

    There are some tracts in human cord that do re-grow (sorry, missed the names, but the corticospinal cord was not one of them. But you knew that.)

    The human cord has about 20 million axons; cats have about 500,000. Only 10% of the cord is needed for locomotion in rat, cat, and human. Most people with sci have 5 to 10% of their cord intact. This means that adding 5% of the axons is often enough for recovery. If you have a growing tumor in the cord, and it takes up 90% of the cord, you may not notice nothing.

    There's a guy up on 76th street who cuts the thinnest slices of lox you can imagine; I've seen tumor removal patients who had thinner sections than that, and they walked out of the hospital. This made me believe early that if I only had to restore 5%, I could do it.

    Graph up of percent of white matter sparing versus walking score . . . the 10% rule applies. If 10% of myelinated axons survive, the rats can walk.

    Okay, what about the central pattern generator? Locomotion is programmed into the cord, which is why chickens with no heads can run.

    Talking about a dancer named Carey who had only one patch of sensation on one leg; he was ASIA B and it took him 2 years to regain walking. He worked for Wise as a patient liaison who signed up every patient he visited to be in a study.

    -------

    What are the barriers to regeneration?
    The injury site lacks certain cell adhesion milecules and is surrounded by reactive gliosis.
    Time. Axons grow no faster than ahair, lesthan 1 mm per day. we need years of sustained growth.
    Growth Inhibitors. Nogo and chondroitin 6 sulfate proteoglycans stop some axonal growth.

    Effective regenerative therapies have to take on all three of these.

    You put cells into the edge of the injury, not the center, where they can form a bridge. You put in growth factors that will help the cells to grow. And you put in antibodies to the inhibitors.

    What kind of cells? Umbilical cord cells combined with lithium is what Wise has chosen to use, wow, he's speeding through his slides about the effects of lithium combined with umbilical cord blood.

    When they announced these trials, and said they were being done in China, lots of Americans volunteered to go to China. Speed-talking, jeez, Wise.

    The criteria for the US trials is:
    Injury at least 1 year old,

    OKAYYY. . . I have to get the final slides from him because he did the last 12 in about 1 minute. Or less. Posting now and making another post for the QA

  2. #2
    Senior Member Timaru's Avatar
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    Brilliant job Kate!

    Many thanks!

  3. #3
    Thanks!

    How can I apply for the clinical trial at China or US? Will clinical trials be coming to Singapore in future?

  4. #4
    Senior Member kate's Avatar
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    Wise Q and A

    Do the patients need to be able weight bear alone for an hour?

    No, just in a standing frame. Probably achievable for most patients.

    What's the difference between the kind of rehab they do in China vs. the USA?

    This has been the most intense debate we've had . . . in China every patient is pushed to the point of tolerance, which is obviously not the standard. Here we think that 1 hour a day for 3 days a week qualifies as intense. They've landed for the US trial on a standard of 3 hours per day for 3 days a week. All this will be walking, walking, walking. There is no data whatsoever on this subject. In Germany they did 3 hours a day for 5 days a week, which was considered at that time to be very intense.

    Q: If you have a settlement, you're golden, if you're in the VA, you're silver, if you're neither, you're screwed . . . what's the plan to get people into these expensive trials?

    There will be a lot of competition in the coming years. Money will be very tight. What the sci community can do is share the wealth. I see expensive equipment sitting in peoples' homes, and we should be making maximum use of these devices. There will be studies coming out that will justify insurance payment for these devices. It's hard, because it's a very tough question to answer.

    Q: Will there be immunosuppression in your trials?

    It won't be necessary, because we're matching blood in 4 out of 6 HLA categories. In our animal studies the cells do not get rejected.

    Q: will the lithium cause pain?

    Not in our studies. That was one of my primary worries; that lithium would cause pain. we just did an 80 patient study with a randomized placebo control . . . we will have a definitive answer this fall. we don't have any data on transplant plus lithium yet;

    Q: Neurotrophins have been tried in the past and have not worked out very well

    No, I have not seen that in humans . .
    Lithium has been shown to stimulate stem cells in the brain as well as neurotrophins. It's been used for a century in treating the brain and the cord

    Q: Will the patients have to live at the centers?

    During the observational phase, people will have to be at the center 3 times. The patient doesn't have to come for the whole period. we anticipate a 3 day hospital stay, then they'll go home for 12 days, then come back for an intensive 6 week period of locomotor training. Some of the centers will be able to do more patients, but this has been the source of some very intense discussion, but we have not landed on any definitive answer.

    Q: Who is going to pay for this?

    We estimated that the total cost for this phase 3 trial would be $32 million. But we got the company to donate the cells, which brings it down to $24 million. Then on August 12 the FDA changed the rules so that we can recover some of the money from the patients; we're doing local fundraising, we're negotiating with the centers to lower the costs. We are committed to not having MONEY be the reason someone gets turned away.

    We may do it like college admissions, where everyone who qualifies to be admitted is admitted, and then the potential to pay is factored into the cost for each person.

    Q: What would probably be the expense after the trial to a patient?

    We're carrying clinical trial insurance, so nothing. Remember that the trial will be randomized, so a quarter of the patients will get nothing, a quarter will get only lithium, a quarter will get only cord blood cells, and a quarter will get both. We have committed to giving all the participants the full treatment, assuming of course that the full treatment is effective.

    In closing -- we should do this ourselves. I'm sick of waiting. We should not be waiting for a gift from a sugar daddy, or from the NIH, or from a company. I'm tired of waiting for someone who has a conflict of interest to step up. The people who have no conflict of interest in this -- who have in fact a vested interest in this -- are you.

    www.justadollarplease.org

  5. #5
    "I'm sick of waiting" I can relate. Thanks Kate for the updates.
    oh well

  6. #6
    I can tell this was NOT the year for me to stay home. I am so sorry that I did not organize myself to attend this year.

  7. #7
    Thx so much Kate for being our eyes and ears and making it come to life. I can just imagine Wise speaking and I was interested in his statement about the small percentage of cord in use by the spinal cord injured. It is such a hopeful statement and I am proof of it.

    I am a walking quad( very difficult but I manage) a spinal cord tumor took up 95% of my cord C2-C6 with little if any symtoms prior to my op. It was so big when the dura was cut it popped out. I walked out of rehab 2 months later pleasing all my docs and thx to the skills of the late Fred Epstien. My cord in the c spine or what is left of it works but is extremely thin.

    Wise spoke of scarring which I have and chose at this time not to have surgery due to the production of worse scarring and the possibility of a vent, loss of bladder/bowel and leg/hands and ever death.

    Again thanks for the info, I learned so much and all the speakers were wonderful,
    Pam

  8. #8
    Great OP Kate, as is your usual standard.

    "In closing -- we should do this ourselves. I'm sick of waiting. We should not be waiting for a gift from a sugar daddy, or from the NIH, or from a company. I'm tired of waiting for someone who has a conflict of interest to step up. The people who have no conflict of interest in this -- who have in fact a vested interest in this -- are you."

    Exactly Dr. Young.

    For those who hadn't previously read any of the thread, " Patients paying for clinical trials"

    http://sci.rutgers.edu/forum/showthread.php?t=123038

    There are some interesting ideas on how to move this process ahead much faster. It is going to be placed upon the shoulders of those injured to move these ideas forward. We are on the 10 yard line right now. The cells are available. It's a matter of what combination will provide the most benefit.

  9. #9
    Senior Member lunasicc42's Avatar
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    thank you for the good read
    "That's not smog! It's SMUG!! " - randy marsh, southpark

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  10. #10
    Just back to Detroit and wanted to thank everyone who contributed to W2W, it was a great event. Wise's presentation was superb! I would also like to say it was a great pleasure to meet Kate, John, Bruce, and Sue.
    “As the cast of villains in SCI is vast and collaborative, so too must be the chorus of hero's that rise to meet them” Ramer et al 2005

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