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New Treatment Offers Hope for Systemic Sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disorder marked by early skin lesions and the progressive tissue fibrosis.// More than skin deep, this thickening and hardening of connective tissue affects the blood capillaries, the gastrointestinal tract, the lungs, and the heart. In SSc patients, fibrosis frequently leads to organ dysfunction, serious illness, and death. Researchers have yet to determine the underlying cause of this disfiguring, debilitating condition or find an effective anti-fibrotic remedy.

Studies of SSc suggest the central role of two cytokines, transforming growth factor ? (TGF?) and platelet-derived growth factor (PDGF), in the development of fibrosis through stimulating the synthesis of extracellular matrix (ECM) proteins. On the strength of these findings, researchers at the University of Erlangen-Nuremberg, Germany and University Hospital Zurich, Switzerland, set out to test the therapeutic potential for SSc patients of a small growth factor inhibiting molecule widely used in the treatment of leukemia.

Through skin biopsies, researchers obtained fibroblast cultures from the lesions of five patients with SSc, and six healthy sex- and age-matched controls. All the specimens were stimulated with TGF? and PDGF and incubated with the inhibitory molecule, imatinib mesylate. Then, applying real-time polymerase chain reaction and various assays, researchers analyzed and compared the expression of EMC proteins in SSc and normal skin fibroblasts. In addition, they assessed the anti-fibrotic effects of imatinib mesylate on laboratory mice with bleomycin-induced dermal fibrosis compared with non-diseased controls.

On the experimental fibroblast cultures from SSc patients, imatinib mesylate strongly reduced the synthesis of EMC proteins, the number of myofibroblasts, and the thickness of skin, almost back to levels observed in the healthy control groups. Similarly, imatinib mesylate effectively suppressed the deve
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