The ability of the investigational drug crenolanib to inhibit a signaling molecule called PDGF reduced fibrosis in the skin and heart of animal models of systemic sclerosis (SSc), according to a study by researchers at the Boston University School of Medicine.
The study, “Blockade of PDGF receptors by crenolanib has therapeutic effect in patient fibroblasts and in preclinical models of systemic sclerosis,” appeared in the Journal of Investigative Dermatology.
Previous studies have shown that overactivation of cells called fibroblasts is largely what causes fibrosis. When these cells are hyperactivated, they produce an excess of cellular matrix collagen, which subsequently causes fibrosis to develop.
The signaling molecule PDGF, or platelet-derived growth factor, is involved in the fibrotic process, along with its receptor (PDGFR). However, the extent both are involved in fibrosis isn’t clear.
Using a selective PDGFR inhibitor called crenolanib, which is now being tested to treat several cancers, the team evaluated the role of these signaling molecules in the development of fibrosis. They found that inhibiting PDGFR blocked the proliferation and migration of human fibroblasts. Indeed, a more detailed analysis showed that inhibition of PDGFR also reduced the expression of two known active participants on the fibrotic process, periostin and CCN2. Researchers further confirmed this after evaluating the expression of these molecules in skin biopsies from 33 diffuse cutaneous SSc patients and 15 healthy control subjects.
To address this matter in a more relevant clinical setting, researchers treated SSc animal models with crenolanib. This reduced fibrotic lesions on the animals’ skin and heart. Taken together, the results suggest that PDGF and its receptor are potential targets for SSc therapy.
“Because crenolanib is already used in clinical trials with good safety records, this study strongly supports the testing of crenolanib as a therapy for patients with SSc,” wrote Maria Trojanowska, corresponding author of the study.
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