GED-0507 as a novel anti-fibrotic treatment option for pulmonary fibrosis

Background: Idiopathic Pulmonary fibrosis(IPF) is a progressive, irreversible and fatal disease. Approved drugs( Pirfenidone[Pir] and Nintedanib[Nin]) slow down functional decline but do not halt or reverse the disease. Aim: to assess the efficacy of GED-0507 (GED), a compound with anti-inflammatory and anti-fibrotic effects, in a mouse model of bleomycin-induced pulmonary fibrosis(BIPF). Methods: C57BL/6 mice were sacrificed 28 days after a single intratracheal instillationof bleomycin(BLM) (0.8 mg/kg). Oral GED (100 mg/kg/d) was compared to Pir (400 mg/kg/d) or Nin (60 mg/kg/d) given in preventive (n=105) or therapeutic mode (n=45). Efficacy measures included mortality rate, weight loss, macroscopic pulmonary lesions and deposition of collagen and α-smooth muscle actin (αSMA). TGF-β, collagen, αSMA, fibronectin, TNF-α, IL-1β and MUC5b mRNA levels were measured by RT-PCR. Results: At day 28, BLM-induced mortality and weight loss rates were 55% and 11%, respectively, in untreated mice. Prophylactic GED reduced by 80% BLM-induced mortality (p Conclusions: GED reduces significantly the severity of BIPF and is more efficacious than optimal concentrations of Pir and Nin in this setting.