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Thread: oral drug for spinal cord injury improves movement in mice

  1. #1

    oral drug for spinal cord injury improves movement in mice

    http://www.eurekalert.org/pub_releas...-fod010713.php

    First oral drug for spinal cord injury improves movement in mice, study shows

    COLUMBUS, Ohio – An experimental oral drug given to mice after a spinal cord injury was effective at improving limb movement after the injury, a new study shows.

    The compound efficiently crossed the blood-brain barrier, did not increase pain and showed no toxic effects to the animals.

    "This is a first to have a drug that can be taken orally to produce functional improvement with no toxicity in a rodent model," said Sung Ok Yoon, associate professor of molecular & cellular biochemistry at Ohio State University and lead author of the study. "So far, in the spinal cord injury field with rodent models, effective treatments have included more than one therapy, often involving invasive means. Here, with a single agent, we were able to obtain functional improvement."

    The small molecule in this study was tested for its ability to prevent the death of cells called oligodendrocytes. These cells surround and protect axons, long projections of a nerve cell, by wrapping them in myelin. In addition to functioning as axon insulation, myelin allows for the rapid transmission of signals between nerve cells.

    The drug preserved oligodendrocytes by inhibiting the activation of a protein called p75. Yoon's lab previously discovered that p75 is linked to the death of these specialized cells after a spinal cord injury. When they die, axons that are supported by them degenerate.

    "Because we know that oligodendrocytes continue to die for a long period of time after an injury, we took the approach that if we could put a brake on that cell death, we could prevent continued degeneration of axons," she said. "Many researchers in the field are focusing on regeneration of neurons, but we specifically targeted a different type of cells because it allows a relatively long therapeutic window."

    An additional benefit of targeting oligodendrocytes is that it can amplify the therapeutic effect because a single oligodendrocyte myelinates multiple axons.

    A current acute treatment for humans, methylprednisolone, must be administered within eight but not after 24 hours after the injury to be effective at all. An estimated 1.3 million people in the United States are living with spinal cord injuries, experiencing paralysis and complications that include bladder, bowel and sexual dysfunction and chronic pain.

    The experimental drug, called LM11A-31, was developed by study co-author Frank Longo, professor of neurology and neurological sciences at Stanford University. The drug is the first to be developed with a specific target, p75, as a potential therapy for spinal cord injury.

    The research is published in the Jan. 9, 2013, issue of The Journal of Neuroscience.

    Researchers gave three different oral doses of LM11A-31, as well as a placebo, to different groups of mice beginning four hours after injury and then twice daily for a 42-day experimental period. The scientists analyzed the compound's effectiveness at improving limb movement and preventing myelin loss.

    The spinal cord injuries in mice mimicked those caused in humans by the application of extensive force and pressure, resulting in loss of hind-limb and bladder function and experimentally calibrated baseline difficulty in walking and swimming.

    The researchers determined that the mice did not experience more pain than the placebo group at all the doses tested, suggesting that LM11A-31 does not worsen nerve pain after spinal cord injury.

  2. #2
    How do they measure pain in mice or rats?

  3. #3
    I would love to try this pill. Sadly it seems to only protect the myelin and not regrow it.
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  4. #4
    Senior Member Tim C.'s Avatar
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    INeed, your screen name immediately ..

    Quote Originally Posted by ineedmyelin View Post
    I would love to try this pill. Sadly it seems to only protect the myelin and not regrow it.
    INeed, your screen name immediately came to mind as I read this.
    Would it not still require restoration for axons to regrow?

  5. #5
    Quote Originally Posted by Tim C. View Post
    Would it not still require restoration for axons to regrow?
    They're not attempting to restore the damaged axons at the injury site.

    This is just a small molecule tested for its ability to prevent the death of cells called oligodendrocytes at the time of injury. Oligodendrocytes die off for a long period after an injury. The drug preserved oligodendrocytes at the site of injury so there isn't a greater loss. It would be nice to see this acute therapy in the pipeline.

  6. #6
    Quote Originally Posted by Barrington314mx View Post
    How do they measure pain in mice or rats?
    Pain associated behavior (Rats)
    Acute pain and stress are often associated with jumping, freezing, squeaking, biting, escape behavior, and sunken sides (in case of abdominal pain).
    Rats seldom vomit. They are able to passively cast up or regurgitate food. When a rat is 'nauseated', it may repeatedly lift its head in a motion resembling gagging. They can also display pica-behavior, which is defined as eating bedding material or other strange, non-food objects. When rats experience pain, they communicate by squeaking, whistling and screeching, and by producing ultrasound.

    Pain associated behavior (Mice)
    We generally differentiate between acute pain and chronic pain. Acute pain (post-surgery or disease-related) is often characterized by a number of behavioral changes, such as aggression, isolation in the group, restlessness and self-mutilation, as well as by autonomic reactions such as dilated pupils and rapid breathing. With chronic pain, such as seen with tumors, notable effects may be poor overall condition, piloerection, social isolation and a hunched posture. The animals will lose weight and are less active. Diseased mice tend to take in little water, which will lead to rapid dehydration. When mice are in either acute or chronic pain, they may start to engage in pica-behavior, which is defined as eating bedding material or other strange, non-food objects.

    Source:
    Last edited by GRAMMY; 01-09-2013 at 02:01 AM.

  7. #7
    Mices can be sad too?!
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    Interesting. A successful oral treatment may of course meet up with some contraindications, but in general avoids the obvious perils of invasive techniques is this type of treatment, apart obviously from necessary reconstructive following certain types of injury.
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  9. #9
    The OP is a press release article about a scientific abstract written at a basic science research level in mice. The research is published in the Jan. 9, 2013, issue of The Journal of Neuroscience. It is not a human clinical "trial".

  10. #10
    Super Moderator Sue Pendleton's Avatar
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    Quote Originally Posted by GRAMMY View Post
    The OP is a press release article about a scientific abstract written at a basic science research level in mice. The research is published in the Jan. 9, 2013, issue of The Journal of Neuroscience. It is not a human clinical "trial".
    No, but it is easier to get an oral drug to trial than biologics. And yes, another acute treatment could potentially keep people off vents. Hopefully it stays in an oral form.
    Courage doesn't always roar. Sometimes courage is the quiet voice at the end of the day saying, "I will try again tomorrow."

    Disclaimer: Answers, suggestions, and/or comments do not constitute medical advice expressed or implied and are based solely on my experiences as a SCI patient. Please consult your attending physician for medical advise and treatment. In the event of a medical emergency please call 911.

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