Agonizing TNFRSF10B for scleroderma

INDICATION: Scleroderma

Patient sample and mouse studies suggest agonizing TNFRSF10B could help treat scleroderma. In skin samples from patients, mRNA levels of TNFRSF10B were higher than in skin samples from healthy volunteers. In a mouse model of chemical-induced scleroderma, a TNFRSF10B agonistic mAb decreased the skin fibrosis markers of dermal thickening, collagen deposition and myofibroblast accumulation and increased markers of apoptosis in areas of skin fibrosis compared with a control IgG. Also in the model and in a genetic mouse model of scleroderma, TLY012 -- a pegylated recombinant human TRAIL that induces apoptosis by agonizing TNFRSF10B -- decreased dermal thickening, collagen deposition and myofibroblast accumulation and increased markers of apoptosis in areas of skin fibrosis compared with vehicle. Next steps could include testing TNFRSF10B agonists in combination with other antifibrotic agents in the models...