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Thread: Human stem cells delay start of Lou Gehrig's disease in rats

  1. #1
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    Human stem cells delay start of Lou Gehrig's disease in rats

    http://www.eurekalert.org/pub_releas...-hsc101006.php

    Human stem cells delay start of Lou Gehrig's disease in rats

    Public release date: 15-Oct-2006
    Contact: Audrey Huang
    audrey@jhmi.edu
    410-614-5105
    Johns Hopkins Medical Institutions

    Researchers at Johns Hopkins have shown that transplanting human stem cells into spinal cords of rats bred to duplicate Lou Gehrig's disease delays the start of nerve cell damage typical of the disease and slightly prolongs life. The grafted stem cells develop into nerve cells that make substantial connections with existing nerves and do not themselves succumb to Lou Gehrig's, also known as amyotrophic lateral sclerosis (ALS). The study is published in this week's issue of Transplantation.

    "We were extremely surprised to see that the grafted stem cells were not negatively affected by the degenerating cells around them, as many feared introducing healthy cells into a diseased environment would only kill them," says Vassilis Koliatsos, M.D., an associate professor of pathology and neuroscience at Hopkins.

    Although all the rats eventually died of ALS, Koliatsos believes his experiments offer "proof of principle" for stem cell grafts and that a more complete transplant of cells - already being planned -- along the full length of the spine to affect upper body nerves and muscles as well might lead to longer survival in the same rats.

    "We only injected cells in the lower spine, affecting only the nerves and muscles below the waist," he noted. "The nerves and muscles above the waist, especially those in the chest responsible for breathing, were not helped by these transplanted stem cells."

    The research team used so-called SOD-1 rats, animals engineered to carry a mutated human gene for an inherited form of ALS. As in human ALS, the rats experience slow nerve cell death where all the muscles in the body eventually become paralyzed. The particular SOD-1 rats in the study developed an "especially aggressive" form of the disease.

    Adult rats not yet showing symptoms were injected in the lower spine with human neural stem cells - cells that can in theory become any type found in the nervous system. As a comparison, the researchers injected rats with dead human stem cells, which would not affect disease progression. Both groups of rats were treated with drugs to prevent transplant rejection.

    The rats were weighed and tested for strength twice a week for 15 weeks. Weight loss, according to Koliatsos, indicates disease onset. On average, rats injected with live stem cells started losing weight at 59 days and lived for 86 days after injection, whereas control rats injected with dead stem cells started losing weight at 52 days and lived for 75 days after injection.

    The rats were coaxed to crawl uphill on an angled plank, and their overall strength was calculated by considering the highest angle they could cling to for five seconds without sliding backwards. While all the rats grew progressively weaker, those injected with live cells did so much more slowly than those injected with dead cells.

    Close examination of the transplanted cells also revealed that more than 70 percent of them developed into nerve cells, and many of those grew new endings connecting to other cells in the rat's spinal cord.

    "These stem cells differentiate massively into neurons," says Koliatsos, "a pleasant surprise given that the spinal cord has long been considered an environment unfavorable to this type of transformation."

    Another important feature of the transplanted cells is their ability to make nerve-cell-specific proteins and growth factors. The researchers measured five-times more of one particular factor, known as GNDF (short for glial cell derived neurotrophic factor) in spinal cord fluid. The transformation of the transplanted cells also may allow them to deliver these growth factors to other cells in the spinal cord through physical connections.

    Cautioning that clinical applications are still far from possible, Koliatsos hopes to take further advantage of his rodents with ALS to learn as much as possible about how human stem cells behave when transplanted.

    ###


    EMBARGOED FOR RELEASE UNTIL SUNDAY, OCT. 15 AT 12:01 A.M. E.D.T.
    The researchers were funded by the National Institutes of Health, the Muscular Dystrophy Association and the Robert Packard Center for ALS Research at Johns Hopkins.

    Authors on this paper are Leyan Xu, Jun Yan, David Chen, Annie Welsh, Karl Johe, Glen Hatfield and Koliatsos of Hopkins, and Thomas Hazel of Neuralstem Inc., of Rockville, Md.

    On the Web:
    http://neuroscience.jhu.edu/VassilisKoliatsos.php
    http://www.alscenter.org/
    More good news from Johns Hopkins.

  2. #2
    Are these HESCs ? ALS is similar to SMA so I hope this might help my son

  3. #3
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    KBK. They used human neural stem cells. Here is the abstract from Transplantation.

    Human Neural Stem Cell Grafts Ameliorate Motor Neuron Disease in SOD-1 Transgenic Rats.

    Original Articles

    Transplantation. 82(7):865-875, October 15, 2006.
    Xu, Leyan 1; Yan, Jun 1; Chen, David 1; Welsh, Annie M. 1; Hazel, Thomas 2; Johe, Karl 3; Hatfield, Glen 1; Koliatsos, Vassilis E. 1,3,4,5,6

    Abstract:
    Background. Experimental therapeutics for degenerative and traumatic diseases of the nervous system have been recently enriched with the addition of neural stem cells (NSCs) as alternatives to fetal tissues for cell replacement. Neurodegenerative diseases present the additional problem that cell death signals may interfere with the viability of grafted cells. The adult spinal cord raises further challenges for NSC differentiation because of lack of intrinsic developmental potential and the negative outcomes of several prior attempts.

    Method. NSCs from human fetal spinal cord were grafted into the lumbar cord of SOD1 G93A rats. The differentiation fate of grafted NSCs and their effects on motor neuron number, locomotor performance, disease onset, and survival trends/longevity were assessed. Trophic mechanisms of observed clinical effects were explored with molecular and cellular methodologies.

    Result. Human NSCs showed extensive differentiation into neurons that formed synaptic contacts with host nerve cells and expressed and released glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. NSC grafts delayed the onset and progression of the fulminant motor neuron disease typical of the rat SOD1 G93A model and extended the lifespan of these animals by more than 10 days, despite the restricted grafting schedule that was limited to the lumbar protuberance.

    Conclusion. NSC grafts can survive well in a neurodegenerative environment and exert powerful clinical effects; at least a portion of these effects may be related to the ability of these grafts to express and release motor neuron growth factors delivered to host motor neurons via graft-host connections.
    Source.

  4. #4
    © 2006 Independent News and Media Limited

    http://news.independent.co.uk/world/...cle1876678.ece

    Stem cells could be used to reverse symptoms of motor neurone disease
    By Steve Connor, Science Editor
    Published: 16 October 2006

    The prospect of treating motor neurone disease and other forms of severe paralysis has come a step closer with a study showing that it is possible to alleviate symptoms with the help of stem cells.

    Scientists have shown that human stem cells can be used to treat laboratory rats suffering from the same degeneration of the nerve cells in the spinal cord and brain that causes motor neurone disease in people.

    The disease affects about 5,000 people in Britain and life expectancy for most patients is just two to five years. Professor Stephen Hawking, the Cambridge cosmologist and author of A Brief History of Time, is a notable exception, having lived with the condition for more than 35 years.

    Motor neurone disease affects the nerves that control muscle movements throughout the body. It leaves people unable to walk, talk or feed themselves, but their intellect usually remains unaffected.

    The latest research shows that human stem cells can be grafted into the lower spinal cord of specially bred rats with a genetic defect that mimics the human disease. Stem cells can grow into any of the specialised cells of the body - such as nerves or blood cells - and could be used to treat a range of degenerative diseases.

    Vassilis Koliatsos, an associate professor of pathology and neuroscience at Johns Hopkins Medical Institutions in Baltimore, Maryland, said that the transplanted stem cells developed into mature nerve cells and made substantial connections with other cells.

    "We were extremely surprised to see that the grafted stem cells were not negatively affected by the degenerating cells around them, as many feared introducing healthy cells into a diseased environment would only kill them," Dr Koliatsos said.

    The study, published in the journal Transplantation, showed that rats injected with live human stem cells started to lose weight on average at 59 days and lived for 86 days after injection.

    This compared with a second group of "control" animals that were injected with dead stem cells who lost weight at 52 days and lived for 75 days after injection.

    Dr Koliatsos said that rats with the live cell transplants were able to retain their muscle control for longer than the second group of controls. A microscopic investigation showed that 70 per cent of the injected stem cells had developed into nerve cells and many of those grew nerve endings connecting to other cells in the rat's spinal cords.

    "These stem cells differentiate massively into neurones - a pleasant surprise given that the spinal cord has long been considered an environment unfavourable to this type of transformation," Dr Koliatsos said.

    The scientists only injected stem cells into the lower spinal cord, which would not have helped the paralysis of the upper body muscles. Further studies with more extensive transplants are planned before human trials can be carried out.

    "The nerves and muscles above the waist, especially those in the chest responsible for breathing, were not helped by these transplanted stem cells," Dr Koliatsos said.

    The prospect of treating motor neurone disease and other forms of severe paralysis has come a step closer with a study showing that it is possible to alleviate symptoms with the help of stem cells.

    Scientists have shown that human stem cells can be used to treat laboratory rats suffering from the same degeneration of the nerve cells in the spinal cord and brain that causes motor neurone disease in people.

    The disease affects about 5,000 people in Britain and life expectancy for most patients is just two to five years. Professor Stephen Hawking, the Cambridge cosmologist and author of A Brief History of Time, is a notable exception, having lived with the condition for more than 35 years.

    Motor neurone disease affects the nerves that control muscle movements throughout the body. It leaves people unable to walk, talk or feed themselves, but their intellect usually remains unaffected.

    The latest research shows that human stem cells can be grafted into the lower spinal cord of specially bred rats with a genetic defect that mimics the human disease. Stem cells can grow into any of the specialised cells of the body - such as nerves or blood cells - and could be used to treat a range of degenerative diseases.

    Vassilis Koliatsos, an associate professor of pathology and neuroscience at Johns Hopkins Medical Institutions in Baltimore, Maryland, said that the transplanted stem cells developed into mature nerve cells and made substantial connections with other cells.

    "We were extremely surprised to see that the grafted stem cells were not negatively affected by the degenerating cells around them, as many feared introducing healthy cells into a diseased environment would only kill them," Dr Koliatsos said.

    The study, published in the journal Transplantation, showed that rats injected with live human stem cells started to lose weight on average at 59 days and lived for 86 days after injection.

    This compared with a second group of "control" animals that were injected with dead stem cells who lost weight at 52 days and lived for 75 days after injection.

    Dr Koliatsos said that rats with the live cell transplants were able to retain their muscle control for longer than the second group of controls. A microscopic investigation showed that 70 per cent of the injected stem cells had developed into nerve cells and many of those grew nerve endings connecting to other cells in the rat's spinal cords.

    "These stem cells differentiate massively into neurones - a pleasant surprise given that the spinal cord has long been considered an environment unfavourable to this type of transformation," Dr Koliatsos said.

    The scientists only injected stem cells into the lower spinal cord, which would not have helped the paralysis of the upper body muscles. Further studies with more extensive transplants are planned before human trials can be carried out.

    "The nerves and muscles above the waist, especially those in the chest responsible for breathing, were not helped by these transplanted stem cells," Dr Koliatsos said.

  5. #5
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    More from the Scientific American;


    WASHINGTON (Reuters) - Human fetal stem cells can graft onto the spines of rats and delay some of the paralyzing symptoms of motor neuron disease, commonly known as Lou Gehrig's disease, U.S. researchers reported on Monday.

    The new cells were resistant to the disease, also known as amyotrophic lateral sclerosis or ALS, the researchers said.

    <sci>

    The researchers only transplanted cells into the lower spinal cords of the rats, in part because the animals are so tiny and the job is tricky, said Johe. Because the upper spinal cord controls the upper half of the body including breathing, there was no chance of curing the rats.

    "They do develop symptoms and also they still die, but the onset is more slowly developing and the longevity is extended," Johe said in a telephone interview.

    They injected the human fetal stem cells into adult rats not yet showing symptoms and also killed some of the stem cells and injected them into other rats to act as a control.

    On average, the rats treated with live stem cells started losing weight -- one of the first symptoms of disease -- after 59 days and they lived for 86 days. In contrast, the rats given the sham treatment started to lose weight at 52 days and only lived for 75 days.

    While all the rats grew steadily weaker, the treated rats maintained their ability to crawl up a slope for much longer than untreated rats.

    After the rats died the researchers examined their spines and saw that 70 percent of the transplanted cells had developed into nerve cells.

    Johe said the company was growing and nurturing the cells and hoped to create many batches of purified cells that could be used for transplants for a range of patients with spinal cord diseases or injuries.

    "If we see in a year ... really significant effects (in rats) then I think we could be ready for a (human) clinical trial in another year after that," Johe said.

    Source.

  6. #6
    Thanks Leif, atleast they dont say human applications are decades away.

  7. #7
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    KBK. Maybe you want to shoot off an email to Karl Johe of Neuralstem Inc. and ask about your son’s condition in light of this research. If so, here can you find the email address. http://www.neuralstem.com/index.asp?pgid=3
    Last edited by Leif; 10-18-2006 at 07:31 PM.

  8. #8
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    Ha ha, Neuralstem Inc also have a CEO Blog, the "Anti Stem Cell Bluff Called"; http://www.neuralstem.com/eBlog/default.asp?Display=2

  9. #9
    What a brutal disease.

    Whatever it takes, this needs to be escallated quick.

    J.
    And the truth shall set you free.

  10. #10
    Thanks Leif, I sent an email. I will post if I get a reply. My son has been stable since his last hospitalization in Feb. We hope the winter is mild and he remains healthy. He is on a trial drug, I dont see any big gain in strength but compared to other children he is slightly better in terms of movement.

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