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Thread: Neurogenesis and Neurodegeneration

  1. #1

    Neurogenesis and Neurodegeneration

    Until recently, scientists believed that that no new neurons are produced in the brain after death. In other words, we were born with the neurons that we died with. As we grow older, the number of neurons decline and therefore we suffer from loss of neurological function. Some people have earlier losses of neurons. For example, people with amyotrophic lateral sclerosis or Alzheimer's disease would undergo a period of accelerated neuronal loss that we still don't understand.

    About a decade ago, Kemperman & Gage (1997) discovered that the brain is able to make neurons, particularly in certain parts of the brain such as the hippocampus, and possibly in other parts of the brain such as the brainstem and the spinal cord. This process is called neurogenesis. Animal studies suggest that injury accelerates neurogenesis. There is hope that treatments that increase neurogenesis can be used to treat neurodegenerative disorders (Source).

    Unfortunately, although the search for the causes of neurodegeneration have yielded several genes that are known to cause Alzheimer's, amyotrophic lateral sclerosis (ALS), and Huntington's disease, little progress has been achieved in identifying therapies that prevent progression of these diseases. This has been one of the most frustrating aspects of the research in this area.

    The gene underlying one familial form of ALS is an abnormal form of the enzyme superoxide dysmutase (SOD). SOD is known to play a role in breaking down superoxide, a well known oxygen free radical. However, treatments with antioxidants and even SOD itself have not yet proven to be useful for preventing or slowing down the progress of ALS in animals or humans. An estimated 20,000 people in the United States have ALS and about 5000 are diagnosed each year
    (Source).

    This failure to find a cure for ALS despite knowing the gene that causes it raises major questions. How is this possible? It is true that only about 20% of people with ALS have the gene mutation for SOD1 but if the SOD1 gene is inserted into a mouse, the mouse develops a motor degenerative disease. The speculation is that the SOD1 is misfolded and forms aggregates that interrupts other cell function. Recent research is using RNAi (an inhibitory form of RNA) to shut down the production of the mutant SOD1 protein (Source).

    Kerr, et al. (2006) recently causes a great deal of excitement when he reported sucessful use of human embryonic stem cells to replace motoneurons in rats that had been infected with a virus that attacked motoneurons. When the cells were combined with other treatments that promoted regeneration, they showed that the new motoneurons sent out axons into the ventral roots of the spinal cord and reinnervated muscle (Source). Kerr pointd out that they needed the combination of all the treatments in order to restore function.

    The Kerr study was the first to combine human embryonic stem cells for cellular replacement with regenerative therapies to regrow axons from the motoneurons to reinnervate muscle. The study showed improved recovery and survival in the rats. However, it is important to point out that the treatment did not completely restore function and that the model used was a virus-induced motoneuronal degeneration. Kerr is now conducting experiments in a large animal model (pig) and hopes to submit his results to the US FDA for approval of a clinical trial to treat infants with a degenerative motoneuronal disease called spinal muscular atrophy (SMA) which is uniformly fatal.

    A recent article by Liza Gross discussed the difficulties that Douglas Kerr faces in getting the treatments that he has tried in rodents into clinical trial.
    • The first was funding. Federal funding for such research is prohibited for those cell lines that he would like to use for the treatment. Although Maryland approved $15 million for such research, this is a one time appropriation.
    • The second is the lack of cell lines that are genetically compatible for transplantation. Even though Dr. Kerr says that he would be "set to go" if he had 10 cell lines that are "genetically normal", and has not come into contact with animal products, there is the unanswered question whether these cells will be rejected if transplanted.
    • The third is the use of the other treatments in the combination. Dr. Kerr will need to obtain permission to use the combination therapies that he used in his animal studies. These include rolipram, dibutyryl cAMP, cethrin, and other therapies. He would have to convince the companies that make these drugs to provide them. Or else, he has to make the drugs himself and assess their safety.

    The above are tasks that are usually carried out by the therapeutic industry. They contract out safety studies to be carried out by professionals in other companies. They do the manufacturing and validation of the chemicals. They do the safety studies. These types of studies are quite expensive and commands a lion's share of the industry costs of developing a treatment for clinical trial and beyond. Most university laboratories are not well-equipped, funded, or experienced in such work.

    Wise.
    Last edited by Wise Young; 02-20-2007 at 12:23 AM.

  2. #2
    So what your saying is it's too expensive?

    Or is it that it isn't going to stop the disease process unless the process is genetic in origin and some gene tweeking is also performed?

    Isn't SMA genetic in origin?

    Why are some forms of SMA and ALS slow moving and others so damn fast and fatal?
    Would it be a good study to see if at least there is someway of slowing down the fatal type?

    IF Dr. Kerr were to formulate enough cells to do a continuous cell change wouldn't that help slow down the ravage of the fatal types of MND?

    Would two weeks or a month of Iraq war monies help?

    Dr. Wise shouldn't the March of Dimes, Easter Seals, and Crippled Childrens be promoting funding for research in Type 1 SMA? Couldn't we get them to do it?
    Life isn't about getting thru the storm but learning to dance in the rain.

  3. #3
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    What one needs are governments that say that they will cure SCI. Then government will provide funding for the works. Why can’t governments just say that they will provide a cure say for cancer, SCI and diabetes? What is the point of NIH and similar if they wont aim for the bulls eye instead of circling around? Why can’t they simply just say that within a decade we will have a cure for the above? Seems to me no one has control over what’s going on (this not specially directed towards the US, seems to be the case all over the plate). I would think if gov’s really wants to cure SCI they should call a spade for a spade and aim for that in sound projects instead of loosing both money and valuable time like it is now conducted with scattered research not coordinated. In other projects one give the project names, and like here the project name should have been a SCI cure. I think most of them politicians really do not care or they are not updated on the issue in task.

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    Banned Faye's Avatar
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    Quote Originally Posted by Leif
    What one needs are governments that say that they will cure SCI. Then government will provide funding for the works. Why can’t governments just say that they will provide a cure say for cancer, SCI and diabetes? What is the point of NIH and similar if they wont aim for the bulls eye instead of circling around? Why can’t they simply just say that within a decade we will have a cure for the above? Seems to me no one has control over what’s going on (this not specially directed towards the US, seems to be the case all over the plate). I would think if gov’s really wants to cure SCI they should call a spade for a spade and aim for that in sound projects instead of loosing both money and valuable time like it is now conducted with scattered research not coordinated. In other projects one give the project names, and like here the project name should have been a SCI cure. I think most of them politicians really do not care or they are not updated on the issue in task.
    Nixon declared war on cancer.

    "There’s far too much unthinking respect given to authority,” Molly Ivins explained; “What you need is sustained outrage.”
    Kerr, Keirstead, McDonald, Stice and Jun Yan courageously work on ESCR to Cure SCI.

    Divisiveness comes from not following Christopher Reeve's ESCR lead.
    Young does ASCR.
    [I]I do not tear down CRPA, I ONLY make peopl

  5. #5
    Banned Faye's Avatar
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    Quote Originally Posted by Wise Young
    A recent article by Liza Gross discussed the difficulties that Douglas Kerr faces in getting the treatments that he has tried in rodents into clinical trial. • The first was funding. Federal funding for such research is prohibited for those cell lines that he would like to use for the treatment. Although Maryland approved $15 million for such research, this is a one time appropriation.
    • The second is the lack of cell lines that are genetically compatible for transplantation. Even though Dr. Kerr says that he would be "set to go" if he had 10 cell lines that are "genetically normal", and has not come into contact with animal products, there is the unanswered question whether these cells will be rejected if transplanted.
    • The third is the use of the other treatments in the combination. Dr. Kerr will need to obtain permission to use the combination therapies that he used in his animal studies. These include rolipram, dibutyryl cAMP, cethrin, and other therapies. He would have to convince the companies that make these drugs to provide them. Or else, he has to make the drugs himself and assess their safety.

    The above are tasks that are usually carried out by the therapeutic industry. They contract out safety studies to be carried out by professionals in other companies. They do the manufacturing and validation of the chemicals. They do the safety studies. These types of studies are quite expensive and commands a lion's share of the industry costs of developing a treatment for clinical trial and beyond. Most university laboratories are not well-equipped, funded, or experienced in such work.

    Wise.
    Well, stem cell treatment testng is an entirely new field. what may have been the paradigm for biotech in the past may not be so here.

    Funding is a matter of getting some interested philanthropists: Bloomberg for example.....Kerr has a very promising platform.....

    It actually looks quite positive, rather than dismal like you depict it.

    Do you have a link to the Liza Gross article?

    "There’s far too much unthinking respect given to authority,” Molly Ivins explained; “What you need is sustained outrage.”
    Kerr, Keirstead, McDonald, Stice and Jun Yan courageously work on ESCR to Cure SCI.

    Divisiveness comes from not following Christopher Reeve's ESCR lead.
    Young does ASCR.
    [I]I do not tear down CRPA, I ONLY make peopl

  6. #6
    Banned Faye's Avatar
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    Quote Originally Posted by Faye
    Do you have a link to the Liza Gross article?
    I found it!!!

    http://biology.plosjournals.org/perl...l.pbio.0050032


    This is what I like about Kerr!!!
    Kerr won't qualify for federal funding if he uses non-approved lines, but he's not willing to risk the potential problems with the federally sanctioned lines. And adult stem cells aren't an option.

    "There’s far too much unthinking respect given to authority,” Molly Ivins explained; “What you need is sustained outrage.”
    Kerr, Keirstead, McDonald, Stice and Jun Yan courageously work on ESCR to Cure SCI.

    Divisiveness comes from not following Christopher Reeve's ESCR lead.
    Young does ASCR.
    [I]I do not tear down CRPA, I ONLY make peopl

  7. #7
    Quote Originally Posted by Faye
    Well, stem cell treatment testng is an entirely new field. what may have been the paradigm for biotech in the past may not be so here.

    Funding is a matter of getting some interested philanthropists: Bloomberg for example.....Kerr has a very promising platform.....

    It actually looks quite positive, rather than dismal like you depict it.

    Do you have a link to the Liza Gross article?
    Sorry, I just added the link to the article and it is
    http://biology.plosjournals.org/perl...l.pbio.0050032

    I hope that I am not being "dismal" about the situation. I am just discussing the problems that scientists and clinicians are facing in moving stem cell therapies of neurodegenerative disorders. These are real problems.

    Bloomberg gave a huge amount to Johns Hopkins and Doug Kerr should be getting some benefit from that. In the meantime, CIRM (California Institute of Regenerative Medicine) is seriously investing into the resources needed to get a diverse supply of cells.

    Wise.

  8. #8
    Super Moderator Sue Pendleton's Avatar
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    Quote Originally Posted by Wise Young
    I hope that I am not being "dismal" about the situation. I am just discussing the problems that scientists and clinicians are facing in moving stem cell therapies of neurodegenerative disorders. These are real problems.

    Bloomberg gave a huge amount to Johns Hopkins and Doug Kerr should be getting some benefit from that. In the meantime, CIRM (California Institute of Regenerative Medicine) is seriously investing into the resources needed to get a diverse supply of cells.

    Wise.
    No, Wise, you are not being dismal just realistic. And Mayor Bloomberg has been incredibly generous to Hopkins and all those who will need stem cells to be well again. What we need is a targeted $5 million. By targeted I mean the $5 million is solely for spinal paralysis (which includes SMA1). With that Dr Kerr's group, the Maryland part anway, can get us to cure rrials. The trials will cost more but once a phase 1 works funding should be easier.
    Courage doesn't always roar. Sometimes courage is the quiet voice at the end of the day saying, "I will try again tomorrow."

    Disclaimer: Answers, suggestions, and/or comments do not constitute medical advice expressed or implied and are based solely on my experiences as a SCI patient. Please consult your attending physician for medical advise and treatment. In the event of a medical emergency please call 911.

  9. #9
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    Quote Originally Posted by Faye
    Nixon declared war on cancer.
    Yes but Nixon got impeached, can you think of another one that also should be?

  10. #10
    Banned Faye's Avatar
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    Quote Originally Posted by Sue Pendleton
    No, Wise, you are not being dismal just realistic. And Mayor Bloomberg has been incredibly generous to Hopkins and all those who will need stem cells to be well again. What we need is a targeted $5 million. By targeted I mean the $5 million is solely for spinal paralysis (which includes SMA1). With that Dr Kerr's group, the Maryland part anway, can get us to cure rrials. The trials will cost more but once a phase 1 works funding should be easier.
    I wonder how much Kerr's group is getting from the 100 million Bloomberg donation for ESCR.

    But it would be quite something if Kerr succeeds in starting clinical trials right here in the US, at a lower expense than the 50 million needed for ChinaSCINet's phase 1/2 trials.

    "There’s far too much unthinking respect given to authority,” Molly Ivins explained; “What you need is sustained outrage.”
    Kerr, Keirstead, McDonald, Stice and Jun Yan courageously work on ESCR to Cure SCI.

    Divisiveness comes from not following Christopher Reeve's ESCR lead.
    Young does ASCR.
    [I]I do not tear down CRPA, I ONLY make peopl

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