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Thread: Dr. Douglas Kerr - Stem cells regrow damaged nerves in rats: study

  1. #21
    Scratch that, a score by Sweden by Larson in the 90th minute to tie it!

  2. #22
    Quote Originally Posted by flamecarcanet
    actually, looks like Ljungberg gets a yellow and England is set to win...

    sorry. TOPIC! TOPIC! TOPIC! gooooo TOPIC!
    I like him for his extra-curriculars hehe

    sorry KERR KERR KERR!

    Drats, Robinson was atrocious

  3. #23
    Senior Member Max's Avatar
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    Hopkins Scientists Use Embryonic Stem Cells, New Cues To Awaken Latent Motor Nerve Re

    Hopkins Scientists Use Embryonic Stem Cells, New Cues To Awaken Latent Motor Nerve Repair
    Johns Hopkins Medicine
    6/20/2006 11:48:32 AM

    In a dramatic display of stem cells’ potential for healing, a team of Johns Hopkins scientists reports that it has engineered new, completed, fully working motor neuron circuits -- neurons stretching from spinal cord to target muscles -- in paralyzed adult animals.

    The research, in which mouse embryonic stem (ES) cells were injected into rats whose virus-damaged spinal cords model nerve disease, shows that such cells can be made to re-trace complex pathways of nerve development long shut off in adult mammals, the researchers say.

    "This is proof of the principle that we can recapture what happens in early stages of motor neuron development and use that to repair damaged nervous systems," says Douglas Kerr, M.D., Ph.D., a neurologist who led the Johns Hopkins team.

    "It’s a remarkable advance that can help us understand how stem cells can begin to fulfill their great promise," says Elias A. Zerhouni, director of the National Institutes of Health.
    "Demonstrating restoration of function is an important step forward, though we still have a great distance to go."

    The researchers created what amounts to a cookbook recipe to restore lost nerve function, Kerr explains. The approach could one day repair damage from such diseases as ALS (Lou Gehrig’s disease), multiple sclerosis or transverse myelitis or from traumatic spinal cord injury, the researchers say. "With small adjustments keyed to differences in nervous system targets," Kerr says, "the approach may also apply to patients with Parkinson’s or Huntington’s disease."

    In a report on the study, to be released online June 26 in the Annals of Neurology, the Johns Hopkins team says 11 of the 15 treated rats gained significant, though partial, recovery from paralysis after losing motor neurons to an aggressive infection with Sindbis virus -- one that, in rodents, specifically targets motor neurons and kills them. The animals recovered enough muscle strength to bear weight and step with the previously paralyzed hind leg.

    Kerr likens the approach to electrical repair. "Paralysis is like turning on a light switch and the light doesn’t go on. The connectivity is messed up but you don’t know where. We’ve asked stem cells to go where needed to fix the circuit."

    For a brief period after a nerve dies, it leaves behind what’s essentially an empty shell, with some scaffolding and non-nerve substances remaining.
    But with ES injections at the right time and place, and by adding the right cues, we’ve learned to restore the biological ’memory’ for growing neurons, which is clearly still in place," he added.

    The motor circuit engineering combines recent discoveries on stem cell differentiation, a growing understanding of early development of the nervous system, and insights into behavior of the nervous system in traumatic injury, Kerr notes.

    "As adults, our cells no longer respond to early developmental cues because those cues are usually gone," says Kerr. "That’s why we don’t recover well from severe injuries. But that’s what we believe we have changed. We asked what was there when motor neurons were born, and specifically what let motor neurons extend outward. Then we tried to bring that environment back, in the presence of adaptable, receptive stem cells."

    In the study, Kerr’s team first pre-treated cultures of mouse embryonic stem cells with growth factors that both increase survival and prompt specialization into motor neurons. Adding retinoic acid and sonic hedgehog protein -- agents that direct cells in the first weeks of life to assume the proper places in the spinal cord -- readied the conditioned ES cells for the motor neuron circuit that starts in the spinal cord. Then, stem cells were fed into the paralyzed rats’ spinal cords.

    Extending new motor neurons in an adult nervous system, however, meant overcoming hurdles. One involved myelin, the fatty material that insulates mature motor neurons. Like the coating on electrical wire, myelin prevents weakening of the traveling electrical impulse and lets it continue long distances. In humans, the myelinated sciatic nerve, for example, exits the spinal cord and extends to the leg muscles it activates, carrying impulses several feet.

    Once laid down, however, myelin inhibits further nerve growth -- nature’s way to discourage excessive wiring in the nervous system.

    "We had to overcome inhibition from myelin lingering in the dead nerve pathways," Kerr explains. Two recently-developed agents, rolipram and dbcAMP enabled that.

    The assorted treatments let the new motor neurons survive, grow through the spinal cord and extend slightly into the outlying nervous system. A second hurdle remained in getting the neurons to skeletal muscle targets.

    As suggested by earlier work by team member Ahmet Hoke on repair in the outlying, peripheral nervous system, the researchers applied GDNF, a powerful stimulator of neuron growth, to the remains of the newly dead sciatic nerve at a point near its former leg muscle contacts. GDNF attracted the extending motor neurons, "luring" them to the muscles.

    To ensure a continuous supply of GDNF, the researchers relied on injected fetal mouse neural stem cells, a known source of the molecule.

    Of some 4,100 new motor neurons created in the spinal cord, roughly 200 exited the cord and 120 reached skeletal muscle, forming typical nerve-muscle junctions, with appropriate, typical chemical markers.

    Microscopically, the neurons and their muscle associations appear identical to natural ones in healthy animals.
    Fifty of the new neurons were found to carry electrical impulses. (Because such testing is time and labor intensive, only a small area of leg muscle was assayed. The improved ability of treated rats, however, suggests more functional neurons are


    http://www.webwire.com/ViewPressRel.asp?aId=15475

  4. #24
    Leif, I don't know what I can say that has not been said already. Let me try.

    In 1999, John McDonald and colleagues at Washington University in St. Louis reported that mouse embryonic stem cells treated with retinoic acid and transplanted into contused spinal cords of rats myelinated axons and improved locomotor function. In 2004, Hans Keirstead and colleagues at UC Irvine reported that human embryonic stem cells treated with retinoic acid and some other factors also myelinated axons in the spinal cord of rats with contusion injury and improved locomotor function. However, neither provided credible evidence of regeneration or neuronal replacement. The mechanism of the recovery is unclear.

    In 2004, Douglas Kerr and his colleagues at Johns Hopkins reported that mouse embryonic stem cells in combination with cAMP or rho antagonists can result not only in motoneuronal replacement but growth of motor axons out the ventral roots. They used a model of motoneuronal damage using a virus. In the most recent study, they showed that combinations of neurotrophic factors help and they found significant functional improvements in the rats. I am very encouraged by this work and suggest that they indicate that motoneuronal replacement will be possible in people with motoneuronal losses, such as polio. It is not yet clear that this can be applied to people with amyotrophic lateral sclerosis but, given the desperation of this disease, there is significant pressure for a clinical trial of embryonic stem cells in this disease.

    I have not a chance to read the entire article (because I am still travelling in China) and will comment further when I can.

    Wise.

    Quote Originally Posted by Leif
    Dr Wise. Thank you very much for your explanations although brief as I can understand since I understand you are in China doing important work for SCI in the network you have established over there. - As you know, I’m a bit exited about ESCR (embryonic stem cell research) regardless if it’s from mouse embryos or hESC’s. This excitement is not based upon my own bias, but researchers here at home likewise in reports and like you that believe that this cell system has great promises for neuro degenerative injuries and illnesses, especially for the case of creating new motor neurons. Of course researchers here at home don’t say this is Pandora’s Box, but they think that especially for some type of injuries like the ones that I have (SCI with loss of motor neurons and neurons in general) that this is an avenue that should be explored. Those are my words though and should not be translated directly to the words of the researchers I refer to as such (this due to my bad English when it comes to regenerative medicine). Above that I find a lot of exiting things happening these days, like Stephen Davies work, and work as you explained above and not limited to that but your endurance in the field of this research for a treatment for SCI as well.

    – I have questions or more like a query - if you could give us a little more meat to the bone for the research you touched base with above. When you have some spare time could you please write an overview of the work by Dr. Keirstead and Dr. Kerr and others when it comes to ESC’s and treatments for SCI in light of the recent news. I’m not that much of a scientist but it would have been greatly appreciated if you could give us and lecture on the usage of those cells we now have heard about for some time, including what you mentioned above here – the tracts of the cord. Is it possible that axons can use and find ways trough already existing tracts although “dead”, or can as some say, axons find new ways to the i.e. muscles and also signalling back to the brain trough those tracts, not only trough plasticity in the cord but all the way to ignite muscles. Sorry for long post asking the same questions, but I hope you understand my query. Thanks upfront and all the best of luck in China.

    PS. Lynnifer; We will take care of the Moose later (smile), I have to go back and watch World Cup England and Sweden, I enjoy it very much but I take time from anything I like to listen to important research for helping out for SCI.

    When you have time Wise, please give an overview on this research. Thanks upfront.
    Last edited by Wise Young; 06-20-2006 at 07:02 PM.

  5. #25
    Thanks Dr Wise, this gives a lot of hope for my son who has SMA.

    Kavita

  6. #26
    KBK,

    I hope so, too.

    Wise.
    Last edited by Wise Young; 06-20-2006 at 07:01 PM.

  7. #27
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    Dr. Wise thanks. But like me, I don’t’ need only re-myelination. As far as I have studied my own case although it was not due to an injury I have a spot in my cord that I would have liked to understood (this also some says it’s not there). This due to me has little functions therein as such (legs and from T4 and down). I personally believe that this and similar studies is not a fix. but still, when I hear about new motor neurons I’m listening. Also, I know this is basic research, which I believe we need more of. But still – motor neurons; is it possible to create it in humans down the road? And how could this happen?
    Last edited by Leif; 06-20-2006 at 07:28 PM.

  8. #28

    This is really getting a lot of news coverage

    It is good because there was just a front page article about me relating to SCI Cure on the front page here in the local paper, I am going to try and find a way to post it on the site here. The timing of this could not be better though, at least here locally.

    Edited to say, wow, that was simple enough, went to the newspaper website and it was right on the front page. http://newportdailynews.com/articles...news/news1.txt
    Last edited by Curt Leatherbee; 06-20-2006 at 08:38 PM.

  9. #29
    Quote Originally Posted by Wise Young
    Leif, I don't know what I can say that has not been said already. Let me try.

    In 1999, John McDonald and colleagues at Washington University in St. Louis reported that mouse embryonic stem cells treated with retinoic acid and transplanted into contused spinal cords of rats myelinated axons and improved locomotor function. In 2004, Hans Keirstead and colleagues at UC Irvine reported that human embryonic stem cells treated with retinoic acid and some other factors also myelinated axons in the spinal cord of rats with contusion injury and improved locomotor function. However, neither provided credible evidence of regeneration or neuronal replacement. The mechanism of the recovery is unclear.

    In 2004, Douglas Kerr and his colleagues at Johns Hopkins reported that mouse embryonic stem cells in combination with cAMP or rho antagonists can result not only in motoneuronal replacement but growth of motor axons out the ventral roots. They used a model of motoneuronal damage using a virus. In the most recent study, they showed that combinations of neurotrophic factors help and they found significant functional improvements in the rats. I am very encouraged by this work and suggest that they indicate that motoneuronal replacement will be possible in people with motoneuronal losses, such as polio. It is not yet clear that this can be applied to people with amyotrophic lateral sclerosis but, given the desperation of this disease, there is significant pressure for a clinical trial of embryonic stem cells in this disease.

    I have not a chance to read the entire article (because I am still travelling in China) and will comment further when I can.

    Wise.
    Thank you Dr. Wise & have a safe trip to China.
    Vito.

  10. #30
    Senior Member Schmeky's Avatar
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    My wife said this was on the national news this evening (I was not home at the time) and she told me the news media indicated this is 5 years away from human application.

    I laughed.

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