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NIH researchers create comprehensive collection of approved drugs to identify new therapies
Date:4/27/2011

fects. Thalidomide was then repurposed for use against leprosy, an infectious disease causing skin lesions and multiple myeloma, a cancer of plasma cells, which are a type of white blood cell present in bone marrow.

Based on the drug's new application, the U.S. Food and Drug Administration approved thalidomide for the treatment of leprosy in 1998 and for multiple myeloma patients in 2006.

More recently, a team of NHGRI researchers used a similar approach, examining patient blood samples to see what gene and protein networks were active in a syndrome called periodic childhood fever associated with aphthous stomatitis, pharyngitis and cervical adenitis or PFAPA. PFAPA causes monthly flare-ups of fever, accompanied by sore throat, swollen glands and mouth lesions.

The researchers detected overactive genes in the patient's immune response, including interleukin-1, a molecule that is important in triggering fever and inflammation. From these data, the researchers hypothesized that anakinra, a drug that prevents interleukin-1 from binding to its receptor, could be therapeutic. They injected anakinra into five children on the second day of their PFAPA fevers and all showed a reduction in fever and inflammatory symptoms within hours.

Another approach that does not require a complete knowledge of a disease or drug mechanism uses high-throughput drug screening technologies that screen drugs for biological activity in cell-based models of disease. Drugs that record an activity are known as hits and can be further studied for their therapeutic potential by researchers in animal models of the disease and eventually in human clinical trials.

NCGC already has screened the approved drug collection against more than 200 cell-based models of disease. In every screen, NCGC characterizes the pharmacology of each compound over a wide range of concentrations using its signature quantitative high-throughput screening approach. All of the
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Contact: Geoff Spencer
spencerg@mail.nih.gov
301-402-0911
NIH/National Human Genome Research Institute
Source:Eurekalert

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