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

A new study led by researchers at Hospital for Special Surgery identifies the mechanism by which a cell signaling pathway contributes to the development of rheumatoid arthritis (RA). In addition, the study provides evidence that drugs under development for diseases such as cancer could potentially be used to treat RA. Rheumatoid arthritis, a systemic inflammatory autoimmune disease that can be crippling, 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. The study appears online in advance of print in Nature Immunology.

Prior to this study, researchers knew that an intracellular molecular pathway called Notch is involved in diseases such as cancer. In the last year, other scientists conducted a genome wide association study to identify genes that were linked to the development of rheumatoid arthritis. They discovered 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 Dr. Hu. Working with researchers at other institutions in the United States and abroad, HSS investigators started putting two and two together and noted that Notch might be involved in a misfiring of the immune system that is commonly seen in RA.

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 which can also cause inflammation. Macrophages that have gone 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 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.


'/>"/>

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

Related medicine news :

1. Scientists discover distinct molecular subtype of prostate cancer
2. Scientists study serious immune malfunction
3. Scientists discover marker to identify, attack breast cancer stem cells
4. CNIO scientists successfully test the first gene therapy against aging-associated decline
5. Scientists make breakthrough in bile duct cancer with discovery of new gene mutations
6. A*STAR scientists discover switch to boost anti-viral response to fight infectious diseases
7. Scientists Map Melanomas Genome
8. Scripps Research scientists show how memory B cells stay in class to fight different infections
9. Joslin scientists identify important mechanism that affects the aging process
10. NIH scientists link quickly spreading gene to Asian MRSA epidemic
11. Warwick scientists uncover how checkpoint proteins bind chromosomes
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Scientists identify new target to battle rheumatoid arthritis
(Date:6/24/2016)... ... ... People across the U.S. are sharpening their pencils and honing their writing ... which patients and their families pay tribute to a genetic counselor by nominating him ... Genetic Counselors (NSGC) Annual Education Conference (AEC) this September. , In April, Genome ...
(Date:6/24/2016)... York, NY (PRWEB) , ... June 24, 2016 ... ... publication Haute Living, is proud to recognize Dr. Barry M. Weintraub as a ... that “the most beautiful women in the world, and the most handsome men, ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... actively feeding the Frederick area economy by obtaining investment capital for emerging technology ... past 2½ years that have already resulted in more than a million dollars ...
(Date:6/24/2016)... ... June 24, 2016 , ... Venture Construction Group (VCG) ... held on June 20th at the Woodmont Country Club at 1201 Rockville Pike, ... organization dedicated to helping service members that have been wounded in battle and their ...
(Date:6/24/2016)... ... June 24, 2016 , ... Advanced Plastic Surgery ... Arizona pageant as its official Medspa Sponsor. Dr. Josh Olson, a board-certified plastic ... , Dr. Olson says the decision to support the pageant in an ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 2016 Research and Markets ... Electronics 2015-2025: Applications, Technologies, Forecasts" report to ... In-Mold Electronics, Smart Skin, Structural Health Monitoring, Composite ... Structural electronics involves electronic and/or electrical components and ... dumb structures such as vehicle bodies or conformally ...
(Date:6/24/2016)... Research and Markets has announced the addition of the ... to their offering. ... World Market for Companion Diagnostics covers the world market for ... report includes the following: , World IVD ... (N. America, EU, ROW), 2015-2020 , World IVD Companion ...
(Date:6/24/2016)... Tenn. , June 24, 2016  Arkis ... providing less invasive and more durable cerebrospinal fluid ... in funding.  The Series-A funding is led by ... Lighthouse Fund, and other private investors.  Arkis, new ... neurosurgical instrumentation and the market release of its ...
Breaking Medicine Technology: