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Scientists identify new target to battle rheumatoid arthritis
Date:5/20/2012

inflammatory macrophages attack joints and they produce inflammatory mediators that basically sustain inflammation in joints," said Dr. Hu.

In experiments, researchers found that knockout mice that lack the Notch pathway in macrophages were unable to produce certain type of macrophages and exhibited a lesser inflammatory phenotype.

"Notch is essential for the development and function of a cell type called the inflammatory macrophages and if this pathway is missing in mice, then you don't get good differentiation of the inflammatory macrophages," said Dr. Hu. In a nutshell, the Notch pathway is essential for the differentiation and function of inflammatory macrophages, and these macrophages are critical for human RA pathogenesis.

In a series of test tube studies, the researchers flushed out the specifics of how Notch influences the molecular cascade that leads to generation of inflammatory macrophage. In another experiment, the investigators used an inhibitor of the Notch pathway called GSI-34 that is under development and showed that this drug could inhibit the function of macrophages.

The researchers say the study provides the first explanation of how Notch contributes to rheumatoid arthritis pathogenesis. It also shows, for the first time, that investigational Notch inhibitors under development for cancer and Alzheimer's could potentially be used to treat RA. Several Notch inhibitors are under development by various companies and a few are currently in Phase III trials.

"Before this study, the Notch pathway has been implicated mainly in cancer, but in this study we define how it is connected to RA," said Dr. Hu.


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Contact: Phyllis Fisher
fisherp@hss.edu
212-606-1724
Hospital for Special Surgery
Source:Eurekalert  

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