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Thread: Who Plans to Attend Working 2 Walk 2011 ?

  1. #251
    Hi Grammy,

    Since we lesion adult rats at about 6 months of age and then let them go a year before treatment, they are already entering their golden ages. What might be the equivalency in years of age between a rat and a human we really don't know. However, most people use 4-6 weeks as their supposed "chronic" time point after injury but I have been skeptical of this (I would call this sub-chronic). So we decided to leave no doubt that we were studying animals at chronic time points and try something rather unprecedented. I think anybody would agree that a full year after SCI qualifies as a chronic injury. why animals should recover better after chronic injury than they do at acute stages as a result of plasticity (not regeneration) brought about by the enzyme treatment is a matter of speculation which I can address at W2W. But this is good news, indeed.

  2. #252
    Senior Member GJ2's Avatar
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    Who's up for a dinner on saturday evening @ hooters about 1.5 blocks from the hotel ?

    Walking or Rolling Directions

    0.2 mi, 4 mins
    Rockville Pike
    0.2 mi, 5 mins
    Halpine Rd and Rockville Pike
    Walking directions to 1584 Rockville Pike, Rockville, MD 20852

    Hilton Washington DC/Rockville Executive Meeting Center
    1750 Rockville Pike
    Rockville, MD 20852
    1. Head northwest on Rockville Pike toward Halpine Rd
    Destination will be on the right
    0.2 mi

    1584 Rockville Pike
    Rockville, MD 20852

  3. #253
    Quote Originally Posted by jsilver View Post
    Good morning,

    We used our C2 hemisection model to paralyze the hemidiaphragm in female sprague-Dawley rats. This is the same model we used in our nature article (July 14). When we administered ch'ase acutely to the phrenic nucleus region in this model, recovery of diaphragm function never exceeded 10-20% of normal. However, surprisingly, when we administer ch'ase one year after the same lesion, the return of function (which begins within one week) is 40-50% of normal. to my knowledge this is the first time that return of meaningful function to a paralyzed muscle has been reported so long after cord injury. all we did was to use 1 tiny injection of the enzyme and we haven't even begun to push the animals to breath harder using an acute intermittent hypoxia regimen that we have developed. thus, the results may get much better with respiratory therapy. whether this result will translate to other motor systems still has to be studied but I don't see why the respiratory system should be the only one to respond this way. I will discuss our theories to explain why recovery is actually better the longer you wait after injury, but this is certainly wonderful news for the chronically injured.
    Is it your opinion that the motor system for walking may respond in the same way albeit more complicated? Walking is supposed to be to a certain extent a reflex pattern.

  4. #254
    While we don't tend to focus on walking in my lab, I can only speculate that, indeed, certain basic aspects of walking and forepaw function could be improved with the simple enzyme injection coupled with appropriate physical therapy even at chronic stages. There is already substantial evidence that this combination works well at acute stages and James Fawcett has published a nice paper showing that 1 month following incomplete SCI ch'ase plus exercise can result in behavioral improvements in locomotion and paw function equal to that seen following immediate acute treatment. Both the British group and my group are now moving towards the use of contusive injury models with the added benefit of new and improved delivery methods for the enzyme. We have now perfected two contusive injury models in rats ( one at cervical level 2 and one at thoracic level 8). The cervical level injury compromises breathing without killing the animal and the thoracic injury which is much stronger compromises walking and bladder function. It will only be a matter of a relatively short amount of time before we start examining animals at progressively longer time points after injury. Liz Bradbury is already showing that the untoward behavioral consequences on walking of severe contusive injuries can be partially reversed with just the enzyme when delivered using a new lenti-viral delivery approach. Exercise therapy added to the treatment is now in the works. It is clear that big lesions need longer and more widespread exposure to the enzyme.

  5. #255
    Dear Dr. Silver ,
    Hi, hope you are doing well. Thanks for your reply to my last post. My understanding is that there are many dogs that they have sustained spinal cord injury because of accidents , etc (i don't know any of them personaly , but i know many years ago one researcher was trying to help those dog with spinal cord injury with his research which i think it was FES TRANSPLANT or something like that , and i don't know the outcome .etc ) ; Anyway , I assume that most of their owners would be more than happy to see any treatments that might have a chance to help their dogs to get some functions back and reduce their suffering. My question is ,would your lab consider applying your treatment of chondroitinase or the combinations of nerve graft and chondroitinase to those spinal cord injured dogs? I assume no injury is more " natural" than dogs who sustained " natural spinal cord injry" and are chronic injury (depending to the lenght of their injury) . Do you think this is a good idea applying your research on those dogs which are higher animal and are naturally spinal cord injured and if it works on those dogs , it probably will work on human too ?

    Another question : Does DECORIN do exactly the same thing as chondritinase when it comes to treatment of chronic spinal cord injury ? If the answer is yes , Is there any patent for DECORIN too , or anybody can take decorin to clinical trial ?

    Thanks so much indeed for your time and reply.
    Last edited by kz; 10-14-2011 at 11:21 AM.

  6. #256
    kz, I don't know the answers to all of your questions, but awhile back I was reading about the dog/veternarian spinal cord injury work taking place at Purdue. http://www.vet.purdue.edu/cpr/sci.html

    http://www.vet.purdue.edu/cpr/clinical_trials.html

    http://www.vet.purdue.edu/cpr/what_we_do.html

    http://www.vet.purdue.edu/cpr/in_the_news.html

    Dogs with spinal cord injuries before and after treatment with polyethylene glycol (PEG). Dr Pete Laverty
    http://www.sciencentral.com/articles...e_id=218392473



    Last edited by GRAMMY; 10-14-2011 at 11:49 AM.

  7. #257
    Dear Kz and Grammy,

    Very few SCI research groups have used a dog model for cord injury for a couple of reasons. 1) While SCI in dogs does occur due to a variety of reasons, just as it does in humans, the resulting injury is not standardized (just as it is not standardized in human). While this situation in dogs does mimic what happens in people quite well, the lack of a reproducible injury so that one can compare experimental versus control groups is essentially impossible. At our early stages of investigation we have to convince people that we, in fact, have an effect at all. So we have to use a lesion that is equivalent in all animals. Of course, if a therapy is to be successful in people it is going to have to be potent enough to be therapeutic in the treatment of broad variety of injuries and cord levels. so the dog trial would be interesting a quite valuable. However, it looks like companies and the FDA are getting on board for approving stem cell trials for human SCI directly from the rat studies, which is a bit scary. 2) Dogs are actually not a great behavioral model for SCI because their motor skills with their paws/legs are relatively limited. For behavioral investigations of the return of motor function rats are great and cats are also quite good. the equipment for studying respiration and bladder/urinary function have all beed designed for rat. 3) the Purdue study of paralyzed dogs was undertaken by a guy named Richard Borgens, who believed that DC currents passed along the length of a cord injury could restore walking. I haven't heard much about this in many years and the story was always what I would call "fringe" science. Lots of hype but not much believable data. 4) the decorin story has still not been independently replicated as far as I know but from the limited amount of data its effects are meagre compared to those of ch'ase.

  8. #258
    Ps. The PEG story is totally bogus.

  9. #259
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    Quote Originally Posted by jsilver View Post
    Ps. The PEG story is totally bogus.
    Good I'm out of anti-freeze and didn't want to have it anyway!

  10. #260
    Quote Originally Posted by jsilver View Post
    Ps. The PEG story is totally bogus.
    Thanks you. It's more than helpful for someone to point out the discrepancy. Sorting the facts from the fiction helps us to focus on the good solid research that is being done. There always seems to be so much information that is misleading or totally false. Thanks for helping us understand this. Polyethylene Glycol (PEG) liquid is actually used in my closed circuit geo-thermal heating/cooling system. I can't imagine using that on SCI.
    Last edited by GRAMMY; 10-14-2011 at 03:07 PM.

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