Systemic sclerosis (SSc) is one of two rare, chronic autoimmune disorders that affect connective tissue and are known collectively as- scleroderma. Like its counterpart, called localized scleroderma, SSc is marked by thickening or scarring of skin. But unlike that the more benign localized disease, SSc is potentially fatal, as it can progress beyond skin to damage internal organs, among them heart, kidneys, esophagus muscles, or joints.
Researchers generally attribute tissue thickening (and ensuing damage to small blood vessels) to hyperactivation of skin cells called fibroblasts. Normally, fibroblasts are key players in beneficial inflammation associated with wound healing, but when hyperactive, they produce high levels of collagen, leading to chronic inflammation and tissue destruction.
Besides high doses of a moderately effective drug called cyclophosphamide, no treatment can slow SSc scarring. SSc is, in fact, considered an “orphan disease,” meaning that it affects such a small number of patients (an estimated 100,000 in the US in 2015) that pharmaceutical companies are actively not targeting it.
Nonetheless, LJI researcher Nunzio Bottini, M.D., Ph.D., hopes to develop an effective treatment for SSc by first identifying molecules present at abnormally high levels in skin biopsies or in dermal fibroblasts from SSc patients. In preliminary experiments his lab discovered that dermal fibroblast from SSc patients express an abundance of signaling proteins known as tyrosine phosphatases. His team is currently exploring a potential connection between the presence of these phosphatases and SSc. The LJI scientists are partnering with the UC San Diego Center for Innovative Therapy, which coordinates translational research relevant to inflammatory disease, to recruit SSc patients to study interaction of phosphatases with other factors that could be targeted in skin fibroblasts.