New Target Indentified In The Battle Against Rheumatoid Arthritis Identified PDF Print E-mail
Wednesday, 23 May 2012 05:44
Researchers have uncovered the mechanism by which a cell signalling pathway contributes to the development of rheumatoid arthritis (RA). The study led by researchers at Hospital for Special Surgery, also provides proof that drugs under development for diseases such as cancer could potentially be used to treat RA.

Rheumatoid arthritis is a systemic inflammatory autoimmune disease that can be crippling and impacts over a million adults in the United States.

"We uncovered a novel mechanism by which the Notch pathway could contribute to RA,” said Xiaoyu Hu, M.D., Ph.D., a research scientist at Hospital for Special Surgery in New York City and principal investigator of the study.

Before this study was carried out, researchers knew that an intracellular molecular pathway called Notch is involved in diseases such as cancer. Last year, other scientists also conducted a genome wide association study to identify genes that were associated to the development of rheumatoid arthritis.

They found that a certain mutation in a gene involved in the Notch pathway puts patients at risk for RA, but nobody knew just how it was involved.

"We were intrigued. Nothing has been known about how the Notch pathway is important to RA," said Hu.

Working with researchers at other institutions in the United States and abroad, HSS investigators started putting two and two together and noted that if Notch might be involved in a misfiring of the immune system that is a common observation in case of RA. After that, the researchers designed experiments to test whether the Notch pathway had an influence on macrophages, a type of white blood cell that is most commonly known for gobbling up pathogens but at the same time can also cause inflammation.

Macrophages that go ‘awry’ possess widespread pro-inflammatory and destructive capabilities that can critically contribute to acute and chronic rheumatoid arthritis.

"In the case of RA, inflammatory macrophages attack joints and they produce inflammatory mediators that basically sustain inflammation in joints," said Hu.

In experiments, researchers found that knockout mice that lack the ‘Notch’ pathway in macrophages were unable to produce certain type of macrophages and displayed 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 Hu.

In short, 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 leading 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 constrain the function of macrophages. The researchers revealed that the study provides the first explanation of how Notch contributes to rheumatoid arthritis pathogenesis.

For the first time, it also shows that the 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 presently 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," Hu added.

Source: ZeeNews (2012)
 
More articles :

» Finding Reliable Health Information Online

As Internet users quickly discover, an enormous amount of health information is available online. Finding accurate and reliable information on genetic and rare diseases among the millions of online sources is a difficult task for almost everyone. We...

» Cancer Drug Shows Promise For Treating Scleroderma

A drug approved to treat certain types of cancer has shown promising results in the treatment of patients with , according to results from an open-label Phase II trial. While the drug's efficacy must be demonstrated in a Phase III trial, the gold...

» 7 Tips For Balancing Rest and Activity

I wanted to help patients and my friends by sharing some helpful tips about Scleroderma, an autoimmune disease in which the body attacks itself by destroying its own cells and functions. The effects of are quite severe and can affect a patient’s...

» Caribbean Autoimmune Diseases 2011 Summit Highlights

On Sunday October 2nd 2011, the Caribbean Investor Network hosted its Caribbean Autoimmune Diseases Summit at the Ballroom of the Hilton Hotel and Conference Centre.The Summit delivered an array of excellent presentations ranging from the common...

» Researchers Identify Core Genetic Switch As A Viable Target For New Scleroderma Treatments

Scleroderma is a rare, autoimmune disease. Often fatal, it causes the fibrosis or thickening of the connective tissue which support the skin and other vital organs within the body, through the overproduction of . The disease currently lacks a cure...

» Understanding Autoimmunity

What is Autoimmunity?One of the functions of the immune system is to protect the body by responding to invading microorganisms, such as viruses or bacteria, by producing antibodies or sensitized (types of white blood cells). Under normal...