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Thread: In a Break with Dogma, Myelin Boosts Neuron Growth in Spinal Cord Injuries

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    In a Break with Dogma, Myelin Boosts Neuron Growth in Spinal Cord Injuries

    https://health.ucsd.edu/news/release...-injuries.aspx

    In a Break with Dogma, Myelin Boosts Neuron Growth in Spinal Cord Injuries
    The molecule inhibits adult axon regeneration, but appears to stimulate young neurons
    May 23, 2018 | Scott LaFee

    Recovery after severe spinal cord injury is notoriously fraught, with permanent paralysis often the result. In recent years, researchers have increasingly turned to stem cell-based therapies as a potential method for repairing and replacing damaged nerve cells. They have struggled, however, to overcome numerous innate barriers, including myelin, a mixture of insulating proteins and lipids that helps speed impulses through adult nerve fibers but also inhibits neuronal growth.

    But in a new paper, published in the May 23 online issue of Science Translational Medicine , researchers at University of California San Diego School of Medicine report that adult rat myelin actually stimulated axonal outgrowth in rat neural precursor cells (NPCs) and human induced pluripotent (iPSC)-derived neural stem cells (NSCs).

    Mark Tuszynski
    Mark Tuszynski, MD, PhD, professor of neuroscience and director of the UC San Diego Translational Neuroscience Institute

    ?It?s really a remarkable finding because myelin is known to be a potent inhibitor of adult axon regeneration,? said Mark Tuszynski, MD, PhD, professor of neuroscience and director of the UC San Diego Translational Neuroscience Institute. ?But that isn?t the case with precursor neurons or those derived from stem cells.?

    Tuszynski?s lab, with colleagues in Germany and Singapore, monitored neurite outgrowth from NPCs and NSCs growing on a myelin substrate in Petri dishes. Neurites are projections from the cell bodies of neurons, either axons (which carry signals outward to other neurons) or dendrites (which receive the signals). In both cases, they found outgrowth enhanced threefold.

    In subsequent studies using rats with spinal cord injuries, the researchers found that rat NPCs and human iPSC-derived NSCs implanted at the injury site both extended greater numbers of axons through adult central nervous system white matter than through gray matter, and preferentially associated with rat host myelin.

    Paring away some of the myelin molecules known to strongly inhibit axonal growth, Tuszynski and colleagues identified a molecule called reuronal growth regulator 1 or Negr1 as a potential mediator between axons and myelin, permitting the former?s growth. Negr1 is involved in the process by which cells attach to neighboring cells and interact. The growth factor plays an important role during embryological development, when neurons are growing rapidly but before myelin begins to have an inhibitory effect.

    ?When we implant neural stem cells into sites of spinal cord injury, they extend tens of thousands of axons out of the injury site for distances of up to 50 millmeters,? said Tuszynski. ?Adult axons on the other hand, when coaxed to grow, extend 100 axons for a distance of one millimeter. These findings identify why axon outgrowth from neural stem cell implants is so much better than injured adult axons.?

    The findings support the developing approach of using neural precursor cells and iPSC-derived stem cells as a viable and promising method for repairing spinal cord injuries, wrote the study authors. More specifically, they point to the need to further investigate the stimulatory effects of myelin on NPCs and NSCs, which ?could potentially be exploited for neural repair after spinal cord injury.?

    Co-authors include: Gunnar H.S. Poplawski, Richard Lie, Matt Hunt, Hiromi Kumamaru, Jacob Robins, Philip Canete, Jennifer Dulin, Cedric Geoffroy, Binhai Zheng, and Grace Woodruff, UCSD; Riki Kawaguchi and Giovanni Coppola, UCLA; Paul Lu, UCSD and San Diego Veterans Administration Medical Center; Michael Schafer and Lutz Mensel, Johannes Gutenberg University, Mainz, Germany.

    Funding for this research came, in part, from the Veterans Administration, the National Institutes of Health (NS09881, EB014986), Deutsche Forschungsgemeinschaft, the Bernard and Anne Spitzer Charitable Trust, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the National Institute of Neurological Disorders and Stroke (P30 NS062691).
    "I'm manic as hell-
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    I read a smilar article about a year ago I believe it was by Sam Maddox on the Christopher and Dana Reed website. I really did not understand it much at all at that time. All I ever read was spinal cord creates a scar in a month of the accident and no neurons can grow through there. Now, this article is awesome that young neurons can grow through myelin and this is really great news.

  4. #4
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    Quote Originally Posted by scimike View Post
    I read a smilar article about a year ago I believe it was by Sam Maddox on the Christopher and Dana Reed website. I really did not understand it much at all at that time. All I ever read was spinal cord creates a scar in a month of the accident and no neurons can grow through there. Now, this article is awesome that young neurons can grow through myelin and this is really great news.
    You can go back years on this board and see Dr Young saying they could grow through the scar. A lot of people said they couldn’t. I raken he gets the last laugh.

  5. #5
    Quote Originally Posted by #LHB# View Post
    You can go back years on this board and see Dr Young saying they could grow through the scar. A lot of people said they couldn’t. I raken he gets the last laugh.
    I did not know that. Dr Wise was well ahead of everybody.

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    I got out of the hospital in 2009 and started using CareCure to learn and keep up with research. Even then I felt like it wouldn’t be too long till there was something that helped us. I remember seeing others post that they were told 5 years and 10 or even 15 or 20 years there was nothing. While a may never completely give up I getting close to my 10 year and understand those feelings completely.


    I thought for the last few years, at least the implant that reportedly has people standing, moving paralyzed muscles, improving on or even gaining body functions was getting close. I think they did the first implant 10 years ago and have done a total of 12-15 in Louisville. I know there are a few other groups duplicating or doing their own version but still is years away.


    I’ve seen CDRF post about raising $ for 36 patients for maybe 3 years and also seen Reeves son call this the biggest break thru yet. These tweets make people think they don’t have the $. Isn’t bringing treatments to help SCI the reason they exist.


    It is very very very frustrating.

  7. #7
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    Quote Originally Posted by Lyerly View Post
    I got out of the hospital in 2009 and started using CareCure to learn and keep up with research. Even then I felt like it wouldn’t be too long till there was something that helped us. I remember seeing others post that they were told 5 years and 10 or even 15 or 20 years there was nothing. While a may never completely give up I getting close to my 10 year and understand those feelings completely.


    I thought for the last few years, at least the implant that reportedly has people standing, moving paralyzed muscles, improving on or even gaining body functions was getting close. I think they did the first implant 10 years ago and have done a total of 12-15 in Louisville. I know there are a few other groups duplicating or doing their own version but still is years away.


    I’ve seen CDRF post about raising $ for 36 patients for maybe 3 years and also seen Reeves son call this the biggest break thru yet. These tweets make people think they don’t have the $. Isn’t bringing treatments to help SCI the reason they exist.


    It is very very very frustrating.
    I agree man. I never thought I would see 11 years in this chair. Thought we where that close when I got hurt.

  8. #8
    Quote Originally Posted by #LHB# View Post
    I agree man. I never thought I would see 11 years in this chair. Thought we where that close when I got hurt.
    I am a low level injury so I have full use of everything above my waist. I try to not complain Bc I know a lot of higher injuries would give anything to be what I am. I can’t lie that I get crazy frustrated about my own injury but I just don’t think people understand the devestatjon this injury puts on people and their entire families. Obviously it is a big numbers game and since the SCI population is small, people don’t know.

    i had a weird thought the other day, where I live there is a big opioid, heroin problem and homelessness problem. There is such a big effort to help them here and the few things that try to help SCI get very little attention. I am not saying they don’t deserve attention and help but many of these people chose to abuse pills and or put a needle in their arm and there are churches and groups all over that. I have met people that did nothing wrong and just had luck left them paralyzed from the chest down and little to no function. They need help to do most things. There seems to be littke sympathy for that or people just don’t understand it.

    All the talks about complaints about rising medical costs and we are one of the most expensive things to care for. Also the high rate of unemployment and the reliance on government assistance from our populations. So many reasons they should care more. Every few months it’s an article about the implant or transcutenous stim and countless other stuff and it seems to lead to nothing.

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    Any good news about the two cervical stimulators being developed by Dr Reggie Edgerton (transcutaneous and implanted)? I believe Dr Edgerton said one or both would be FDA approved this year.

  10. #10
    Quote Originally Posted by scimike View Post
    I read a smilar article about a year ago I believe it was by Sam Maddox on the Christopher and Dana Reed website. I really did not understand it much at all at that time. All I ever read was spinal cord creates a scar in a month of the accident and no neurons can grow through there. Now, this article is awesome that young neurons can grow through myelin and this is really great news.
    Keep in mind they're adding Negr1 growth enhancer to the rat NPCs and human iPSC-derived NSCs to get these results. Myelin debris at the injury site is a known inhibitor. The Tuszynski lab has been sorting through various molecules to make cocktails for enhancing cellular implant results in a viable therapy a long time. Their first cocktail had lots of molecules in it (7-10?) in their first paper by Paul Lu showing long distance regeneration in the CNS. They needed to pare it down for any hopes of getting to a human trial. That's what the labs have been working on for quite some time. This article has nothing to do with umbilical cord blood cells.

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