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Autoimmune diseases may succumb to new drug strategy
Date:5/2/2014

New pharmaceuticals to fight autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and psoriasis, may be identified more effectively by adding genome analysis to standard drug screening, according to a new study by a research team led by UC San Francisco and Harvard researchers, in collaboration with Tempero and GlaxoSmithKlein.

In a study reported online April 17, 2014 in the journal Immunity, the scientists combined drug screening with state-of-the-art techniques for analyzing the genome, leading to three small molecules that improved symptoms in a mouse form of multiple sclerosis.

The three potential drug candidates, selected from a large library of screened chemicals, each knocked down the response of Th17 cells, a type of immune cell that drives many autoimmune diseases by attacking normal cells in the body. More specifically, the drugs homed in on an essential molecule within the Th17 cells.

"We examined what makes Th17 cells which play a crucial role in multiple autoimmune diseases distinct from other closely related T cells within the immune system," said Alexander Marson, MD, PhD, a leading T cell expert and member of the UCSF Diabetes Center. "Then we investigated several small molecules that inhibit the development and function of these cells. When the Th17 cells were hit by these molecules we saw less severe multiple-sclerosis-like symptoms in the mice."

The research team, led by Marson and Vijay K. Kuchroo, PhD, an immunologist at Brigham and Women's Hospital in Boston and Harvard Medical School, combined powerful techniques to shed light on a class of protein molecules within cells known as transcription factors.

Drug designers have rarely targeted transcription factors. Each transcription factor binds to DNA at a unique set of locations along the 23 pairs of chromosomes, and thereby influences which genes are turned on and off to trigger the protein production that drives cell
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Contact: Jeffrey Norris
jeffrey.norris@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert

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