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    July 7, 2011

    Thalidomide: Poster Child for Drug Repurposing

    To whet the appetite for next week’s Drug Repositioning Conference & CDD Chaired panel on broadcast live via GoToWebinar w/ Drs. Christopher Lipinski,  David Cavalla, and Noel Southall, we are sharing thoughts on Thalidomide – the “poster child for drug repurposing”.

    Thalidomide, infamous for producing so called “thalidomide babies” in the 1950’s when used for morning sickness, today is widely used for Leprosy and multiple myeloma.   Just in CDD Public – and, of course, there are orders of magnitude more data in private and collaborative vaults, Thalidomide shows up in 10 public data sets today!

    Thalidomide is approaching a billion dollar drug for Celegene and provides a nice example of the collaborative insights from multiple researchers.   Gilla Kaplan’s initial discovery and interest in Thalidomide was for TB and AIDS as described on her website:

    “Dr. Kaplan and her team have shown that thalidomide treatment modifies TNF-Alpha and IL-12 production and can improve outcome in humans with lepromatous leprosy, TB or HIV infection, in animal models of inhalational TB (in mice) and TB meningitis (in rabbits), and in vitroin M.tuberculosis-infected human monocytes. Dr. Kaplan and her team have since developed two classes of novel, synthetic analogues of thalidomide that reduce TNF-Alpha production by 50,000 times more than the parent drug, thalidomide, and with fewer deleterious side effects. Co-treatment with these analogues, in combination with antibiotics, is significantly more efficient in reducing TNF-Alpha production and improving survival of rabbits with experimental TB meningitis than antibiotic treatment alone.”

    To move away from the business aspects, to a more personal account, we are sharing this story from John Sanguinetti on what it is like to live with multiple myeloma thanks to thalidomide and other drugs.  It provides an interesting story from one of a respected entrepreneur who helped evolve how computer chips are designed today.   John underwent a successful bone marrow transplant years ago and he’s still going strong today.  A nice reminder of the personal impact of drug discovery research from John’s life story here is extracted below (ironically the event was a fund raiser to support multiple myeloma collaborative R&D):

    I’ll be at the event and it may be a little awkward because I look pretty healthy. I’m afraid I won’t look like a very good poster child for cancer research. People who know me will only notice a difference in that my hair is now curly. It grew back that way after the transplant. Otherwise, I look perfectly normal.

    There are a lot of new drug treatments being researched right now for Multiple Myeloma including drug cocktails that involve thalidomide and dexamethasone in lieu of chemotherapy. They’re effective, but have a limited duration of effectiveness. They have their share of side effects, but they have fewer global side effects than chemotherapy drugs.

    There are other drugs as well, including Velcade, a proteazome inhibitor to which about 75 percent of patients respond. None of these drugs remain effective for a long time, but while they are, the results are encouraging. I’m convinced that these new types of drugs are the future of cancer therapy.

    My wife and daughter have been very supportive through all of this. It’s been a tremendous benefit to me that my wife is a doctor. I turn to her for advice and information, and her ability to navigate the health care system has certainly been a benefit for me. It hasn’t been easy for her, though, since she knows all the bad things that can happen and has a tendency to assume that they all will. I just trust in research and hope I’ll be one of those who outlives the distribution curve.

    I’ve been about as lucky as you can be with my family in all aspects of my life.

    Here is a quick email update that John kindly sent us upon hearing about this blog and panel:

    I took thalidomide pre-transplant instead of the more standard (at the time) chemo (vincristine & adriomycin), and took thalidomide for a year afterwards as maintenance. I have now been taking revlimid for 2 1/2 years and am currently stable. Revlimid is one of the derivatives of thalidomide that you mentioned. It has become the treatment of choice for multiple myeloma. I hope your panel goes well.

    — John

    This blog is authored by members of the CDD Vault community. CDD Vault is a hosted drug discovery informatics platform that securely manages both private and external biological and chemical data. It provides core functionality including chemical registration, structure activity relationship, chemical inventory, and electronic lab notebook capabilities!

    CDD Vault: Drug Discovery Informatics your whole project team will embrace!

    Tag(s): CDD Blog

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