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Thread: Stephen Davies Update

  1. #951
    Guys,
    Dr Stephen Davies has published a paper in the journal "Brain" in Sept'2010. The Link & Summary are as follows.

    http://brain.oxfordjournals.org/cont...wq304.abstract


    Summary

    Scar tissue at sites of traumatic injury in the adult central nervous system presents a combined physical and molecular impediment to axon regeneration. Of multiple known central nervous system scar associated axon growth inhibitors, semaphorin 3A has been shown to be strongly expressed by invading leptomeningeal fibroblasts. We have previously demonstrated that infusion of the small leucine-rich proteoglycan decorin results in major suppression of several growth inhibitory chondroitin sulphate proteoglycans and growth of adult sensory axons across acute spinal cord injuries. Furthermore, decorin treatment of leptomeningeal fibroblasts significantly increases their ability to support neurite growth of co-cultured adult dorsal root ganglion neurons. In the present study we show that decorin has the ability to suppress semaphorin 3A expression within adult rat cerebral cortex scar tissue and in primary leptomeningeal fibroblasts in vitro. Infusion of decorin core protein for eight days resulted in a significant reduction of semaphorin 3A messenger RNA expression within injury sites compared with saline-treated control animals. Both in situ hybridization and immunostaining confirmed that semaphorin 3A messenger RNA expression and protein levels are significantly reduced in decorin-treated animals. Similarly, decorin treatment decreased the expression of semaphorin 3A messenger RNA in cultured rat leptomeningeal fibroblasts compared with untreated cells. Mechanistic studies revealed that decorin-mediated suppression of semaphorin 3A critically depends on erythroblastic leukaemia viral oncogene homologue B4 and signal transducer and activator of transcription 3 function. Collectively, our studies show that in addition to suppressing the levels of inhibitory chondroitin sulphate proteoglycans, decorin has the ability to suppress semaphorin 3A in the injured central nervous system. Our findings provide further evidence for the use of decorin as a potential therapy for promoting axonal growth and repair in the injured adult mammalian brain and spinal cord.

  2. #952
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    When Dr Davies will start trials and where?

    Now we need trials not much laboratory work. Come fast plz.

  3. #953
    Rabin, I read alot about scar formation at point of damage. You've highlighted this again. Dr Young has a problem with the term scar tissue and formation at the site. I hope he responds to this again and clarifies. anyway , it is good to hear directly from this guy again. Let's just get it done.

    Thanks Rabin

    keeping on

  4. #954
    Senior Member Schmeky's Avatar
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    across acute spinal cord injuries
    Doesn't appear to be for us, this indicates new injuries. I hope this isn't the "the big thing" Davies has been alluding to.

  5. #955
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    Quote Originally Posted by Schmeky View Post
    Doesn't appear to be for us, this indicates new injuries. I hope this isn't the "the big thing" Davies has been alluding to.
    http://www.vimeo.com/19192799

  6. #956
    Senior Member Schmeky's Avatar
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    Didn't hear anything about clinical trials. I first visited Davies lab when he was in Houston Texas 6 years ago. He was saying the same then he is saying now.

    Visited his lab in Colorado nearly 4 years ago, if you'll read my report on what he told me, nothing he indicated has transpired. Nothing.

    Hopefully this will change with his paper that he indicated that should be peer reviewed in the last quarter of 2010, but as of the closing of February 2011, has not occurred.

    This isn't my opinion, this is fact.

  7. #957
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    Schmeky

    I have followed this thread very closely because it seemed that clinical trials were close to starting for chronic SCI injuries.

    At Working 2 Walk in November I talked to Dr. Davies but I didn't get any new information from him.

    I'm very discouraged.

    Roger

  8. #958
    Senior Member KIM's Avatar
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    If all he claims is true a small delay is acceptable.

  9. #959
    Senior Member Schmeky's Avatar
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    If all he claims is true a small delay is acceptable
    I completely agree.

  10. #960
    Dear Schmeky,

    Quote Originally Posted by Schmeky View Post
    Didn't hear anything about clinical trials. I first visited Davies lab when he was in Houston Texas 6 years ago. He was saying the same then he is saying now.
    Did you watch the the video from W2W 2010 all the way to the end?

    In the last 3-4 minutes, Dr. Davies discussed his more recent discoveries concerning Decorin, particularly as they potentially benefit chronics.

    At 22:14, he said that when Decorin alone was infused into the injured spinal cord, they found a 17-fold increase in plasmin, an enzyme which breaks down scar tissue.

    At 22:27, he discussed "What can decorin do to promote axon regeneration in the chronically injured spinal cord?"

    He said they found that Decorin not only increases enzymes (such as plasmin) that break down established scar tissue, but that it can "de-sensitize neurons to scar CSPGs and mylein inhibitors."

    At 23:21 he showed a slide indicating that when adult sensory neurons were transplanted onto adult spinal cord myelin, growth was very poor, but when Decorin was added, axon growth increased nearly five-fold within hours.

    At 23:47 he showed a slide indicating that when adult sensory neurons were transplanted onto inhibitory scar CSPGs, growth was again very poor, but when Decorin was added, axon growth increased nearly 15-fold within hours. To quote Davies:

    "Decorin can directly boost the ability of neurons to grow axons on inhibitory molecules found throughout the chronically injured spinal cord."

    The last three lines from his final slide, concerning his "Ongoing studies":

    Testing human decorin & hGDAsBMP in chronic contusion SCI models

    Combinations of GDAs, Decorin and rehab


    Development of GDAsBMP for future human trials


    He said they were actively working to determine what the most effective combinations are for both acute and chronic human SCI.

    The "Research Projects" section of his faculty page also concludes with:

    "At present we are now developing stem cell based technologies to generate the human form of the GDAsBMP cells with a view to moving use of these cells to human clinical trials as soon as possible."


    Quote Originally Posted by Schmeky View Post
    Visited his lab in Colorado nearly 4 years ago, if you'll read my report on what he told me, nothing he indicated has transpired. Nothing.
    While discussing the two penultimate lines in his last slide, "Testing human decorin & hGDAsBMP in chronic contusion SCI models" and "Combinations of GDAs, Decorin and rehab," Davies said that it had always been his plan to bring these two lines of his research together, and that that had now happened.

    Quote Originally Posted by Schmeky View Post
    Hopefully this will change with his paper that he indicated that should be peer reviewed in the last quarter of 2010, but as of the closing of February 2011, has not occurred.

    This isn't my opinion, this is fact.
    No author can affect, much less control the speed of peer reviewers of his paper and you have no way of knowing whether it in fact happened or not in 2010 -- the reviewers may have responded in the time frame he'd given you with comments requesting further data or other clarifications (it happens all the time with peer reviewed papers) and Davies may be responding to such comments even as I'm typing this, if he hasn't already. You need to understand that peer review can be an extended process and that publication isn't necessarily automatic once it's been completed.

    I'm sure Dr. Davies is extremely anxious to see this paper published and doing everything he possibly can, although that's very little, once it's been submitted for review.

    I have a friend from college who's a medical researcher like Davies (though not in SCI) and another who's married to one. These folks generally work 60-80 hours per week, 50 weeks or more a year -- most are consumed by their work, often to the exclusion or at least significant detriment of their personal lives.

    Someone who's never seen that kind of relentless work schedule up close and over an extended period of time (and a brief visit to a lab simply can't provide any true picture of just how long the hours are that such researchers usually put in, usually for years) would probably have difficulty appreciating the full extent to which these folks so often devote themselves to their work, so I say, "Thank you, Dr. Davies, and thank you, too, Dr. Young, for everything you sacrifice personally for this community in the search for a cure."

    I recall, too, that when Kate was blogging from W2W 2010 in November, she reported that Dr. Davies explained he couldn't say anything about his "big breakthrough" because he had signed a "non-disclosure agreement," which suggests to me that he's found a corporate partner to help fund clinical trials. Journals don't normally require prospective authors to sign such agreements (they just cancel publication if the author blabs publicly, as I understand).

    Consequently, it sounds to me, reading between the lines, that Dr. Davies is busy designing human clinical trials while awaiting publication, but the design process is far from instantaneous, too, as I understand it. If anyone has $650 to spend, they can attend a conference being held next month to educate clinical investigators in the complexities of FDA requirements: http://www.socra.org/html/FDA_Conference.htm


    FriendlySprite

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