Targeting Systemic Sclerosis: From Bioinformatics to Clinical Research PDF Print E-mail
Tuesday, 09 April 2013 21:04
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 Medicine, doctors may be able to treat some patients more effectively.

Characterized by thickening of the skin, SSc can also cause significant complications in the joints and internal organs—particularly the esophagus, lower gastrointestinal tract, lungs, heart and kidneys. There is no cure—and the one drug commonly used to treat the disease, mycophenolate mofetile (MMF) does not work for all patients. In the absence of a biomarker to inform therapeutic medical decisions, patients are exposed to ineffective and potentially toxic medications.

In the first study of its kind in Scleroderma, Michael Whitfield, PhD, associate professor of genetics at the Geisel School of Medicine, and Monique Hinchcliff, MD, MS, assistant professor of medicine at the Feinberg School of Medicine, together have shown that gene expression signatures can accurately identify patients who will positively respond to a particular therapy.

"This is a true translational research project that has progressed from an observation in my lab here at Geisel, to an approach that can influence patient care," says Whitfield. "It's been exciting to see a basic science discovery translated into the clinic so quickly.

"We think this is a great example of the type of translational science that can occur when a team with diverse and complimentary expertise successfully work together to solve a problem," he adds.

Whitfield's and Hinchcliff's findings revealed that patients whose conditions improve with MMF therapy all share a particular gene expression.

During the clinical trial, patients who improved during MMF therapy were classified in the inflammatory gene expression subset, while patients who did not improve were classified in the normal-like or fibroproliferative gene expression subsets. This fits the initial hypothesis since MMF impairs lymphocyte proliferation. A gene expression signature was also identified—the signature was composed of genes whose expression changed significantly during MMF treatment in patients that improved, but was absent in patients that did not.

The results of these experiments suggest that analysis of gene expression in skin may allow targeted treatment in patients with SSc.

While this is a small pilot study, it represents an important step forward in approaching complex rare diseases, such as Scleroderma, where existing therapies show little or no efficacy, notes John Varga, MD, John and Nancy Hughes Professor at Northwestern University Feinberg school of Medicine, who also participated in the study.

"This work is the first to associate a molecular subtype of scleroderma with targeted treatment response, " adds Howard Chang, MD, PhD, Stanford University School of Medicine. "Only patients with a particular molecular subtype benefitted from the drug mycophenolate, and these investigators discovered the gene expression changes that it induces in Scleroderma."

If validated in a larger patient cohort—soon underway—the results will have significant impact on the way we think about the development of effective treatment strategies for patients with systemic sclerosis. Their research paper, "Molecular Signatures in Skin Associated with Clinical Improvement During Mycophenolate Treatment in Systemic Sclerosis," will be published in the Journal of Investigative Dermatology.

Source: Geisel School of Medicine (2013); Targeting Systemic Sclerosis: From bioinformatics to clinical research. Original press release can be found here.

 
More articles :

» Liver Autoantibodies in Patients with Scleroderma

Thelma L. Skare & Renato M. Nisihara & Osvaldo Haider & Pedro M. Azevedo & Shirley R. R. UtiyamaReceived: 5 January 2010 / Revised: 13 August 2010 / Accepted: 26 September 2010# Clinical Rheumatology 2010Association between...

» 5 Cold And Flu Prevention Tips

With some 20,000 cases of flu having been reported in New York state and many more throughout the rest of the United States, many have declared this year's cold and flu season to be of epidemic proportions. According to the , the 2012-13 flu season...

» Coping With Scleroderma

Coping with SclerodermaBy Jane Brandenstein, P.T., University of Pittsburgh Medical CenterAs physical therapists, there are some things that we have learned over the years about Scleroderma, and there are even more things we wish we understood...

» B-Cell Depletion Therapy in Systemic Sclerosis: Experimental Rationale and Update on Clinical Evidence

Dimitrios Daoussis, Stamatis-Nick C. Liossis, Georgios Yiannopoulos, and Andrew P. AndonopoulosDivision of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Rion, 26504 Patras,...

» More Research Needed to Understand Scleroderma

With an estimated 14 million cases worldwide, you would think more would be known about , a chronic, debilitating disease that can lead to the hardening and tightening of skin and connective tissue. But it seems that we don’t know enough: “We...

» The Pain Perspective in Scleroderma

Systemic sclerosis (scleroderma) is a disease in which inflammatory and fibrotic changes result in overproduction and accumulation of and other extracellular matrix proteins, resulting in intimal vascular damage, fibrosis, and occasionally organ...