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Thread: Massive’ Spinal Axon Regrowth Follows Gene Deletion: A Major Advance for Spinal Cord

  1. #1

    Massive’ Spinal Axon Regrowth Follows Gene Deletion: A Major Advance for Spinal Cord

    This is great great news! Dr. Young, what do you think of this?

    Massive’ Spinal Axon Regrowth Follows Gene Deletion: A Major Advance for Spinal Cord Injury Recovery


    Neurology Today
    16 September 2010; Volume 10(18); pp 24-25
    Robinson, Richard

    Outline
    Deletion of a single gene allows axons to grow through a complete spinal cord injury, and to do so in abundance. The discovery, called “spectacular” by another spinal cord injury researcher, appears to overcome a major hurdle in spinal cord repair, and sets the stage for tackling other problems in promoting functional recovery after spinal cord injury.

    The gene, called PTEN (phosphatase and tensin homolog), is an inhibitor of another gene, called mTOR (mammalian target of rapamycin). mTOR is active in the embryonic development of the CNS, but is gradually turned off by PTEN.

    “mTOR controls protein translation, and is required for most forms of cellular growth,” said Zhigang He, PhD, associate professor of neurology at Harvard Medical School, who led the study published online Aug. 8 before the print edition of Nature Neuroscience. “Our finding is very simple. When mTOR is functional, it promotes growth. PTEN inhibits it.”

    In the study, Dr. He turned his attention to spinal cord injury in adult mice. He showed that sprouting of axons above a brainstem lesion was robust in the early post-natal period, but dropped sharply over the next two months. That drop-off correlated with reduced mTOR expression in the injured corticospinal neurons, suggesting a correlation between the mTOR downregulation and the decrease in sprouting.

    Based on his prior studies and on work demonstrating that PTEN inhibits mTOR, Dr. He created mice genetically deficient in PTEN. Neurons in these mice retained the ability to sprout in response to injury, in a manner “characteristic of young neurons,” he said.

    In order to test whether the sprouting neurons can grow past the injury site, Dr. He induced either partial or complete lesions at T8 in these mice. In mice with active PTEN, axons in either type of injury retract from the injury site. “Nothing can regenerate,” he said.


    read...

    http://www.aan.com/elibrary/neurolog...01009160-00003
    Last edited by manouli; 09-24-2010 at 02:17 PM.

  2. #2
    Senior Member
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    Manouli,
    Thank you for all of your efforts keeping us posted. Hopefully, someday I can buy you a drink. I hope we can toast to walking someday.
    Best Regards,
    Joe

  3. #3
    Manouli,

    I can not find enough words to thank you, really ! thank you so much for your efforts. you keep my hoop a live, keep up the good work.
    keep (rolling) Walking

    Please join me and donate a dollar a day at http://justadollarplease.org and copy and paste this message to the bottom of your signature

  4. #4
    Wise, do you know of this researcher? What do you think of the fnding with respect to chronics , particulary on this board? It appears so many things happening; can't wait till we get a chance for improvement.

    Thanks Manouli

    keeping on

  5. #5
    Keeping On - see Wise's comments on this thread:

    http://sci.rutgers.edu/forum/showthread.php?t=138809

  6. #6
    Source:
    After finishing his PhD with me, Kai Liu joined a group at Harvard, headed by Zhigang He. They discovered that a gene called PTEN controls the ability of corticospinal neurons in the cortex to regenerate. If PTEN is knocked out or inactivated by other messengers such as mTOR, corticospinal tracts undergo robust regeneration. PTEN itself acts through other messenger systems such as GSK-3b. He's group has been working on manipualting mTOR. Our group has been working on GSK-3b which is inhibited by lithium (which also stimulates regeneration). At the end of this post, I attach a recent review article that was written by He's group.

    I think that when you read the article, you can perhaps appreciate the complexity of manipulating the PTEN gene, which may do many things besides inhibit regeneration. We chose to study lithium because it has been used for many years to treat manic depression, has been shown to stimulate regeneration in the spinal cord by inhibiting GSK-3b, stimulates neural stem cells to proliferate, and activates umbilical cord blood cells to produce growth factors, and can be taken immediately to clinical trial. (Source)
    Source:
    . . . if you knock out the effects of a gene called PTEN, which allows a gene called mTOR to express, this turns on intracellular messengers that tell corticospinal tract axons to grow. This study showed clearly that shutting off PTEN allows robust regeneration of the corticospinal tract, previously considered the most difficult spinal tract to regenerate.

    It is also of interest that mTOR appears to act by inhibiting GSK-3beta (glycocogen synthetase kinase 3 beta), the same enzyme that lithium shuts down. So, a lot of this is beginning to tie together. We are of course taking umbilical cord blood cells and lithium to clinical trial. (Source)
    Source:
    It will be some time before this treatment can and will be used in clinical trials because PTEN is also an important regulator of cancer. Preventing PTEN expression in the brain is not a trivial thing to do, will require (based on current technology) viral transfection of genes that block the expression of PTEN, and may not work for other spinal tracts besides corticospinal. What is good about this study is that one other laboratory (UC Irvine) has confirmed it and there may be other ways of reducing the effects of PTEN without having to block its expression. For the example, the mechanism by which PTEN blockade works is to upregulate mTOR which in turn blocks GSK3-beta. Lithium blocks GSK3-beta. It is the reason why we are using lithium in clinical trials of chronic spinal cord injury in China. (Source)
    Source:
    This is a "breakthrough". It is the first time that a particular gene has been shown to be responsible for the ability of an important spinal tract to regrow. It shows that the system can regenerate but certain genes hold back certain pathways in adults. They need to ascertain whether these genes are also holding back other neurons (i.e. serotonergic, rubrospinal, vestibulospinal, etc.) but this provides the possibility of the first gene therapy for encouraging regeneration of the spinal cord.

    Please notice that they did not get rid of "scar" when they did this study. They just turned off PTEN which inhibits mTOR. When mTOR is turned on, the axons grew, not only in hemsection but also in the contusion model. Finally, as I pointed out in the other post, mTOR's action is believed to be mediated by inhibition of glycogen synthetase kinase, something that lithium also inhibits. We are of course taking lithium to clinical trial along with umbilical cord blood mononuclear cells. (Source)
    ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

  7. #7
    Fly ; yep. Let's get it on.

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