New Genetic Path Targeted For Scleroderma Therapy PDF Print E-mail
Monday, 19 March 2012 18:53
A genetic pathway previously known for its role in embryonic development and cancer has been identified as a target for systemic sclerosis, or scleroderma, therapy. The finding, discovered by a cross-disciplinary team led by John Varga, MD, John and Nancy Hughes Distinguished Professor of Rheumatology at Northwestern University Feinberg School of Medicine, was recently published in the journal Arthritis & Rheumatism.

"We showed, for the first time, that the Wnt signaling pathway is abnormally activated in scleroderma patients," said Varga, who is also a physician at Northwestern Memorial Hospital. "This is significant for three reasons. First, it gives a better picture of scleroderma and fibrosis in general. Second, it provides a strategy for assessing disease severity, progression, and activity. And third, it opens a door for the design of treatments that aim to block the Wnt pathway and restore its normal controlled activity."

Varga's laboratory collaborated with a pulmonary team at Northwestern, along with teams at Case Western Reserve University and Dartmouth University on the discovery.

Researchers studied skin and lung biopsies from scleroderma patients and found that the Wnt pathway was 'turned on', in contrast to healthy individuals where the pathway was 'turned off.' Varga said this activation may be due to loss of Wnt inhibitors that normally serve as 'brakes' on the pathway to prevent its activation.

The team also examined what the pathway does using fibroblasts and stem cells from healthy people. They found Wnt causes fibroblast activation and blocks the development of fat cells (adipocytes), which directly contribute to scar formation and tissue damage seen in scleroderma.

"Scleroderma is a complex and poorly understood disease with no cure," said Varga. "Our findings suggest that treatments targeting the Wnt signaling pathway could lead to an effective treatment."

Varga said Northwestern researchers next plan to conduct multi-center preclinical studies to evaluate treatments that block the Wnt pathway in animal models and measure Wnt activity in additional scleroderma biopsies to see if it can be clinically useful as a biomarker.

New genetic path for scleroderma

 
More articles :

» New Study Shows Increased Risk Of Cancer In Scleroderma

patients have a 75% increased risk of cancer compared to the general population, a meta-analysis confirms, leading the authors to recommend screening in these patients.Patients were at particular risk of developing (RR 4.35) and haematological...

» Anticentromere Antibody Positive Sjögren’s Syndrome: A Retrospective Descriptive Analysis

Introduction: A subgroup of patients with primary Sjögren’s Syndrome (SS) and positive anticentromere antibodies (ACA) were recognized as having features intermediate between SS and systemic sclerosis (SSc). Our goal was to describe this group...

» Prevalence and Correlates of Sleep Disturbance in Systemic Sclerosis

Tracy Frech, Ron D. Hays, Paul Maranian, Philip J. Clements, Daniel E. Furst and Dinesh KhannaObjective:Rheumatologic disorders are associated with sleep disturbances. This study examines sleep disturbance correlates in patients with...

» Identification of New Autoantibody Specificities Directed at Proteins Involved in the Transforming Growth Factor Beta Pathway in Patients with Systemic Sclerosis

Guillaume BussoneHanadi DibMathieu TambyCedric BroussardChristian FedericiGenevieve WoimantLuc CamoinLoic GuillevinLuc MouthonArthritis Research &Therapy 2011, 13:R74IntroductionAntinuclear antibodies (ANA), usually detected by indirect...

» Clinical Manifestations of Heart Disease In Autoimmune Disorders

Dr. Lawrence Phillips is the Assistant Professor of Medicine, Division of Cardiology and Director of Nuclear Cardiology at the . At the recently concluded , Dr. Phillips presented on the clinical manifestations of heart diseases in autoimmune...

» Actelion Fibrosis Drug Doesn't Meet Key Endpoint

Actelion Ltd today announced the initial results of BUILD-3, a clinical study evaluating the safety and efficacy of Bosentan in patients suffering from idiopathic pulmonary fibrosis. While there was a consistent trend in favour of Bosentan, the...