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Clofazimine once used for Leprosy proves effective against MS, Type 1 and Psoriasis

Discussion in 'Research' started by Mom2Boys, Feb 23, 2009.

  1. Mom2Boys

    Mom2Boys Approved members

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    I thought this was an intersting article about an old drug being used to possibly treat/cure type 1 diabetes.

    http://www.starbulletin.com/news/20090223_Isle_doctors_find_new_use_for_1890s_drug.html

    Isle doctors find new use for 1890s drug

    In their quest for a drug to combat autoimmune diseases such as multiple sclerosis and diabetes, doctors in Hawaii and on the mainland have stumbled upon an old friend.

    Clofazimine, developed in the 1890s and used for decades against Hansen's disease, or leprosy, has proved effective against MS, type 1 diabetes and the skin condition known as psoriasis.

    "People have been working for years and spending tens of millions of dollars on developing a drug to inhibit a specific molecular target involved in these diseases, and here we have a safe, known drug that hits that target," said Jun O. Liu, a pharmacologist at Johns Hopkins University in Baltimore.

    An old anti-leprosy drug might provide an effective treatment for three devastating autoimmune diseases -- multiple sclerosis, psoriasis and type 1 diabetes -- say two Hawaii researchers and mainland colleagues.

    The finding is reported in the Public Library of Science by Drs. Reinhold Penner and Andrea Fleig of the University of Hawaii John A. Burns School of Medicine and the Queen's Medical Center, and researchers at Johns Hopkins University and Northwestern University.

    They said the antibiotic clofazimine -- developed in the 1890s for tuberculosis -- holds promise as a therapy for autoimmune diseases.

    Clofazimine did not work for TB, but was used successfully against leprosy, the Hawaii researchers explained in an interview. Although no longer needed for that disease in the United States, it is still being developed for use in Brazil and other countries where leprosy remains, said Penner, director of the Queen's Center for Biomedical Research.

    He and Fleig -- world leaders in cellular function research -- found the compound acts against a particular type of ion channel, a potassium channel Kv1.3, in lymphocytes, a type of white blood cell. Working with them at Queen's was UH postdoctoral researcher Suhel Parvez, now in Germany.

    Johns Hopkins researchers stumbled upon clofazimine as a potential treatment for autoimmune diseases while screening more than 3,000 drugs to identify new uses for them, Penner said. The drugs were assembled over seven years in the Johns Hopkins Drug Library.

    The idea was to test old medicines that already have Food and Drug Administration approval (and known side effects) for new disease targets, said Fleig, who heads the Laboratory of Cell and Molecular Signaling at Queen's with Penner.

    Clofazimine was among drugs tested against lymphocytes -- cells that defend the body against alien organisms, parasites and bacteria.

    The drug's "tremendous effect on human immune cells" surprised the Johns Hopkins researchers, pharmacologist Jun O. Liu said in a news release.

    "People have been working for years and spending tens of millions of dollars on developing a drug to inhibit a specific molecular target involved in these diseases, and here we have a safe, known drug that hits that target," Liu said.

    Johns Hopkins contacted Penner and Fleig to find out how clofazimine, thought to be an antibacterial drug, works on human immune cells. They identified the mechanism: It interferes with potassium channel Kv1.3, an important factor in activating lymphocytes, Penner said.

    The discovery has been patented between Queen's and Johns Hopkins, and companies have contacted them about licensing, Penner said.

    Many companies were looking for blockers for ion channel Kv1.3 but could not find anything that did not have a lot of side effects or affect other potassium channels in the body, Penner said.

    "Until today it was completely impossible to use compounds that are working on Kv1.3 specifically without affecting other potassium channels," he said.

    Clofazimine is not the most potent blocker against Kv1.3, and higher concentrations are needed, but it does not affect other potassium channels and has no side effects except a purplish skin discoloration, he said.

    "In any case, this is just the start," Penner said. "It's pure serendipity that this compound appears to be effective in this system."

    The drug now can be modified and optimized so it is more potent, requires a lower concentration and reduces skin problems, he said.

    "The nice thing about this compound is it now can actually enter clinical trials for multiple sclerosis, psoriasis and type 1 diabetes because it's a compound already," Penner said. "It has been through clinical trials already and been used to treat humans. We don't have to start from scratch, although it may not be the best one yet."

    He said the scientists want to optimize clofazimine to use against rheumatoid arthritis and to replace compounds with significant side effects now used to prevent organ rejections in transplants.

    They also are testing other compounds against diseases that involve the immune system. For example, Fleig said, they have identified a blocker for an ion channel they plan to test on a mouse model to see whether they get comparable results for asthma and type 1 diabetes.

    "We're hopeful we can find something beneficial against all sorts of diseases that involve the immune system," Penner said.
     
  2. joshualevy

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    In my mind, every web page, every newspaper article, and every blog entry which discusses research that has been done only on animals, should contain the following warning:

    Warning: this research has been done on animals, not people. Even if wildly successful, it has a less than 1% chance of ever being useful for people, and is more than 10 years away from general use. Do not get your hopes up. This is a long way from you being able to use it, and may never work!

    I've previously blogged about why I think this here:

    Also, my reading of this news article is that they have not proven that Clofazimine is effective against MS, Type 1 or Psoriasis. They have done some analysis that suggests that it might be, but they have not done any experiments to show this.

    Joshua Levy
     
  3. Mom2Boys

    Mom2Boys Approved members

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    Wow, sorry to offend you, but it did specifically say : "The drug's "tremendous effect on human immune cells" surprised the Johns Hopkins researchers, pharmacologist Jun O. Liu said in a news release."

    I take that to mean they did test it on human cells. I know that it doesn't mean that it will necessarily be the cure we all hope for, but it is just another avenue of research that I thought people may find interesting.
     
  4. WestinsMom

    WestinsMom Approved members

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    I personally think he is just on here to promote his blog...IMHO.
     
  5. joshualevy

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    You didn't offend me. You just repeated what the news article said. And I just added on what the news article should have included. Those guys are more then 10 years away from anything we can use; the news article should have made that clear, but it didn't.

    If you look look farther along in the article, there is some more text that makes it sound like they haven't don't any actual testing yet, just computer simulations. However: I agree that one sentence does make it sound like they have done testing on human tissue. But remember, the general flow of experiments goes like this: tissue (human or animal), then animal testing, then human testing. Even if they are in tissue testing, they will need to spend years in animal testing, and then over 10 years in human testing.

    Oh, I agree that it might be interesting. I just wanted to point out that even if interesting it is a very long way off. When researchers talk to newspaper guys, they almost never talk about how far way they are from widespread human use. The newspaper guys then publish articles just like the one you put in, that make it sound like a cure is only a few years away.
    But it's really not. (Or at least not from that article.)

    Joshua Levy
     
  6. jet59or

    jet59or Approved members

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    Research hopes with a grain of salt...

    I think that it is necessary to report any findings. I also think everyone (except the newbies) realizes that anything just reported is going to be a long way off if at all. My son is coming up to his one year anniversary and I can tell you that I hung onto every word for a cure the first few months, but now I'm more realistic... still hopeful but realistic.

    Here is a great article (scroll down to the picture showing the articles) that will put this into perspective!

    http://www.diabetesmine.com/2008/10/diabetes-research-news-—-hype-or-hope-a-call-for-questions.html
     
  7. Becky Stevens mom

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    thank you Mom2boys that was a very interesting article.It always a good thing IMHO to read about new research ideas and theorys thats how cures come about, trying the impossible or improbable until something works. I appreciate your bringing it to our attention
     
  8. fazimib

    fazimib New Member

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    Joshua is right on 10 years average for most compounds. Currently it takes even much longer than 10 years for a compound from lab bench top to the market. Usually a significant time is spent on animal model and phase I clinical trails.
    But clofazimine is special. IT IS A FDA APPROVED DRUG already. That means it has already passed animal model and phase I clinical trail in terms of its toxicity and safety, although it's approved for leprosy only. The next thing need to do is to prove its effectiveness on autoimmune diseases such as type I diabetes and multiple sclerosis. That's why several phase II clinical trail need to validate this assumption.
    If you wiki this drug, you will find this drug already be successful in clinic for lot of autoimmune diseases such as lupus, psoriasis, inflammatory bowl diseases and even in bone marrow transplantation patients! The major problem is that not ALL the patients respond to this drug.
     
    Last edited: Mar 4, 2009
  9. joshualevy

    joshualevy Approved members

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    That's a good point, that I missed. In theory someone could use this right now if they wanted to, as an "off label" use. It will still need to go through phase-II and phase-III testing (plus marketing approval) to get "on label" approval. That would probably take 6-8 years, minimum. The good news is that if the phase-II trials were really successful, people could ask their doctors to proscribe it "off label" right afterward, and hope for the best.

    Joshua Levy
     
  10. Ellen

    Ellen Senior Member

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    Here's a link to the abstract and the full text. I withhold enthusiasm.

    Clofazimine inhibits human Kv1.3 potassium channel...[PLoS ONE. 2008] - PubMed Result

    Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes.

    Ren YR, Pan F, Parvez S, Fleig A, Chong CR, Xu J, Dang Y, Zhang J, Jiang H, Penner R, Liu JO.
    Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
    The Kv1.3 potassium channel plays an essential role in effector memory T cells and has been implicated in several important autoimmune diseases including multiple sclerosis, psoriasis and type 1 diabetes. A number of potent small molecule inhibitors of Kv1.3 channel have been reported, some of which were found to be effective in various animal models of autoimmune diseases. We report herein the identification of clofazimine, a known anti-mycobacterial drug, as a novel inhibitor of human Kv1.3. Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway. These effects of clofazimine provide the first line of experimental evidence in support of a causal relationship between Kv1.3 and calcium oscillation in human T cells. Furthermore, clofazimine was found to be effective in blocking human T cell-mediated skin graft rejection in an animal model in vivo. Together, these results suggest that clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders.
    PMID: 19104661 [PubMed - indexed for MEDLINE]
    PMCID: PMC2602975


    Full text here: Clofazimine Inhibits Human Kv1.3 Potassium Channel by Perturbing Calcium Oscillation in T Lymphocytes
     

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