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Thread: Molecular 'stop signs' may hold secret of nerve regeneration/Spinal cord repair may be possible/Scientists report progress in spinal cord repair

  1. #1
    Senior Member Max's Avatar
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    Molecular 'stop signs' may hold secret of nerve regeneration/Spinal cord repair may be possible/Scientists report progress in spinal cord repair

    Molecular 'stop signs' may hold secret of nerve regeneration
    Using brain cells from rats, scientists at The Johns Hopkins University School of Medicine and the University of Hamburg have manipulated a molecular "stop sign" so that the injured nerve cells regenerate.
    While their findings are far from application in people, the prospects for eventually being able to repair spinal cord injury are brighter, they say.

    "Four thousand years ago, physicians wrote that spinal cord injury was untreatable, and unfortunately it's much the same today," says Ronald L. Schnaar, Ph.D., professor of pharmacology and of neuroscience at Hopkins. "But the basic-science framework for improving this situation is quickly emerging."

    In adult mammals, including humans, molecular signals carefully control the number of contacts nerve cells make by inhibiting new connections. When the brain or spinal cord has been damaged, the goal is to neutralize those inhibitors so that the long tentacles of nerve cells, the axons, might reestablish their broken connections, says Schnaar.

    The research team reports identifying brain chemicals that are involved in the ability of one of the inhibitors to prevent injured nerve cells from connecting to other nerves or muscles. By keeping the chemicals from interacting with the inhibitor, the researchers were able to stimulate damaged nerve cells to regenerate in laboratory dishes. Their report is in the June 11 issue of the Proceedings of the National Academy of Sciences.

    "In the central nervous system, once an axon is interrupted in some way, through disease or injury, generally it's stopped dead in its tracks, but in the rest of the body, damaged axons can re-grow," says Schnaar. "To make headway in treating brain and spinal cord injury, we need to attack this problem from a number of angles, and our studies have provided an additional target for intervention."

    Of the "stop signs" identified so far, Schnaar's team focused on MAG, or myelin-associated glycoprotein, which is part of the myelin wrapping that insulates all nerve cells. Understanding how the newly identified molecules responsible for MAG's inhibitory effect -- called gangliosides -- interact with MAG to send the "stop" signal to the nerve may lead one day to potential treatments, say the scientists.

    In their experiments with rat and mouse cells, Hopkins postdoctoral researcher Alka Vyas tested four ways of stopping MAG and the gangliosides from interacting: destroying part of the ganglioside where MAG usually attaches, limiting the amount of the gangliosides made by the cells, using antibodies to block MAG or using antibodies to block the gangliosides. The research team now is focused on determining exactly how the gangliosides and MAG work together to stop nerve regeneration.


    ###
    The work was funded by the National Institutes of Health, the National Multiple Sclerosis Society and the Stollof Family Fund. Other authors on the report are Himatkumar Patel, Susan Fromholt, Marija Heffer-Lauc, Kavita Vyas and Jiyoung Dang of Johns Hopkins; and Melitta Schachner of the University of Hamburg, Germany.

    On the Web: http://www.pnas.org

    Johns Hopkins Medical Institutions' news releases are available on an EMBARGOED basis on EurekAlert at http://www.eurekalert.org and from the Office of Communications and Public Affairs' direct e-mail news release service. To enroll, call 410-955-4288 or send e-mail to bsimpkins@jhmi.edu. On a POST-EMBARGOED basis find them at http://www.hopkinsmedicine.org.



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  2. #2
    Senior Member Max's Avatar
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    Spinal cord repair may be possible

    Spinal cord repair may be possible
    From the Science & Technology Desk
    Published 6/19/2002 5:57 PM
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    BALTIMORE, June 19 (UPI) -- Scientists announced Wednesday they have figured out a new way to get nerve cells to regenerate in the laboratory and have come one step closer to being able to repair spinal cord injuries -- although that prospect remains years away.

    "For the first time in history there is some optimism that we may be able to get functional recovery of spinal cord injuries," Ronald L. Schnaar, co-author of the study and professor of pharmacology and of neuroscience at Johns Hopkins University, told United Press International. "Whether it's this decade or next decade, I think we'll begin to see this knowledge turned into therapies."

    Schnaar and colleagues at the University of Hamburg, Germany, discovered how to modulate a molecular signal that inhibits the regeneration of nerve cells after they are damaged.

    "Whenever there is an injury to the central nervous system including the spinal cord, molecules remain which instruct nerve cells (not to regenerate)," Schnaar explained. By blocking these molecules or the nerve cell receptors they bind to, "we might be able to allow nerve cells to regenerate."

    One of these inhibiting molecules is called MAG, or myelin associated glycoprotein. Rat nerve cells will grow when placed in a culture dish, but if MAG is added it stops them cold, Schnaar said.

    Schnaar's team found blocking the nerve cell receptors that MAG binds to -- either with an enzyme that shuts off the binding site or an antibody that prevents MAG from binding altogether -- they could get the nerve cells to grow again.

    The findings "point the way to a potential way to enhance nerve regeneration," Schnaar said, cautioning, "Our studies have no immediate medical application, and I think it will be some time before these therapies get tested in humans."

    The findings with MAG mirror studies of two others inhibitor molecules similar to MAG. The molecules, called Nogo and CSPG, or chondroitin sulfate proteoglycan, also can be blocked, allowing nerve cells to regrow after they are damaged.

    "The hope is that by combining one or more of these reversal techniques we can take the brakes off and get nerve cells to regrow," Schnaar said.

    Studies in animals have looked promising and have generated "modest recovery," he said. "For people with spinal cord injury, every modest amount of increase would be important."

    Marie T. Filbin, a professor of neurobiology at Hunter College in the City University of New York, downplayed the findings.

    "It's an interesting hypothesis. However, a lot more work needs to be done to show that (interfering with MAG receptors causes) inhibition," said Filbin, who recently published two papers in the journal Neuron showing the injection of a molecule called cyclic AMP enabled rat spinal cords to regenerate after being cut.

    Filbin's research suggests MAG is binding to something else on the nerve cells and soon will publish research showing just that, she told UPI.

    Schnaar would not provide a timeline for when nerve regeneration therapies might be used in humans, but he said, "People in the field are talking 5 to 10 years. But who knows, it could be faster, it could be slower."

    The study appears in this week's Proceedings of the National Academy of Sciences.

    (Reported by Steve Mitchell, UPI Medical Correspondent, in Washington)

    Copyright © 2002 United Press International

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  3. #3
    Senior Member Max's Avatar
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    Scientists report progress in spinal cord repair

    Scientists report progress in spinal cord repair
    Copyright © 2002
    United Press International

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    United Press International

    BALTIMORE, June 19 (June 19, 2002 7:35 p.m. EDT) - Scientists announced Wednesday they have figured out a new way to get nerve cells to regenerate in the laboratory and have come one step closer to being able to repair spinal cord injuries - although that prospect remains years away.
    "For the first time in history there is some optimism that we may be able to get functional recovery of spinal cord injuries," Ronald L. Schnaar, co-author of the study and professor of pharmacology and of neuroscience at Johns Hopkins University, told United Press International. "Whether it's this decade or next decade, I think we'll begin to see this knowledge turned into therapies."

    Schnaar and colleagues at the University of Hamburg, Germany, discovered how to modulate a molecular signal that inhibits the regeneration of nerve cells after they are damaged.

    "Whenever there is an injury to the central nervous system including the spinal cord, molecules remain which instruct nerve cells (not to regenerate)," Schnaar explained. By blocking these molecules or the nerve cell receptors they bind to, "we might be able to allow nerve cells to regenerate."

    One of these inhibiting molecules is called MAG, or myelin associated glycoprotein. Rat nerve cells will grow when placed in a culture dish, but if MAG is added it stops them cold, Schnaar said.

    Schnaar's team found blocking the nerve cell receptors that MAG binds to - either with an enzyme that shuts off the binding site or an antibody that prevents MAG from binding altogether - they could get the nerve cells to grow again.

    The findings "point the way to a potential way to enhance nerve regeneration," Schnaar said, cautioning, "Our studies have no immediate medical application, and I think it will be some time before these therapies get tested in humans."

    The findings with MAG mirror studies of two others inhibitor molecules similar to MAG. The molecules, called Nogo and CSPG, or chondroitin sulfate proteoglycan, also can be blocked, allowing nerve cells to regrow after they are damaged.

    "The hope is that by combining one or more of these reversal techniques we can take the brakes off and get nerve cells to regrow," Schnaar said.

    Studies in animals have looked promising and have generated "modest recovery," he said. "For people with spinal cord injury, every modest amount of increase would be important."

    Marie T. Filbin, a professor of neurobiology at Hunter College in the City University of New York, downplayed the findings.

    "It's an interesting hypothesis. However, a lot more work needs to be done to show that (interfering with MAG receptors causes) inhibition," said Filbin, who recently published two papers in the journal Neuron showing the injection of a molecule called cyclic AMP enabled rat spinal cords to regenerate after being cut.

    Filbin's research suggests MAG is binding to something else on the nerve cells and soon will publish research showing just that, she told UPI.

    Schnaar would not provide a timeline for when nerve regeneration therapies might be used in humans, but he said, "People in the field are talking 5 to 10 years. But who knows, it could be faster, it could be slower."

    The study appears in this week's Proceedings of the National Academy of Sciences.

    Copyright 2002 by United Press International.

    All rights reserved.

  4. #4
    Four thousand year's ago scientist said we where untreatable,and i hope someone can figure this out when i'am alive,not being negative,someone might figure this out,but me praying someone figure's this out in the next 25yrs and they have been going at it for the last four thousand don't seem to realistic?i've always thought positive and alway's will,but what the hell,where going off a dead end dune

  5. #5
    Senior Member Jeff's Avatar
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    OTL

    There was very little progress up until a decade ago. Although, a surprising amount was known. I wouldn't let the 4000 year thing scare you. It's a new day.

    ~See you at the SCIWire-used-to-be-paralyzed Reunion ~

  6. #6
    I just posted the abstract of the PNAS paper at the Basic Research Forum

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