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 :

» Unite Against Scleroderma

{gallery}unite{/gallery}

» Th22 Cells As Milestone Of Immunological Research

The newly discovered Th22 cells are a previously unknown subset of . T helper cells are white blood cells that help activate other immune cells when the body is infected by viruses or bacteria. At the same time they help the body to tolerate own...

» Caution Needed When Using ACE Inhibitors in Scleroderma

Exposure to angiotensin-converting enzyme inhibitors prior to the onset of renal crisis in patients with increases the risk of death, according to 1-year findings from the prospective observational International Scleroderma Renal Crisis Survey.The...

» Scleroderma Renal Crisis: A Pathology Perspective

Ibrahim Batal, Robyn T. Domsic, Thomas A.Medsger Jr., and Sheldon BastackyInternational Journal of RheumatologyVolume 2010, Article ID 543704Scleroderma renal crisis (SRC) is an infrequent but serious complication of systemic sclerosis (SSc). It is...

» Targeting Systemic Sclerosis: From Bioinformatics to Clinical Research

Systemic sclerosis (SSc), also known as Scleroderma, is a rare autoimmune connective tissue disorder that's difficult to treat. However, thanks to new research at Dartmouth's Geisel School of Medicine and Northwestern University's Feinberg School of...

» Scientists and Clinicians Address Diagnosis and Treatment for Autoimmune and Autoinflammatory Diseases

Autoimmune and autoinflammatory diseases are a major health issue. The National Institutes of Health reports that up to 23.5 million Americans are afflicted. The American Autoimmune Related Diseases Association reports the number is closer to 50...