Pulmonary

Patient sample and mouse studies suggest inhibiting LPAR1-ENPP2 signaling could help treat bronchiolitis obliterans syndrome following lung transplantation. In lung mesenchymal cells from lung transplant patients, ENPP2 levels were higher in patients with bronchiolitis obliterans syndrome than in unaffected patients. In mice engrafted with mesenchymal cells from the bronchiolitis obliterans syndrome patients, mesenchymal cell-specific knockdown of LPAR1 or ENPP2 decreased numbers of fibrotic lesions in the lung compared with normal LPAR1 and ENPP2 expression. In a mouse lung transplant model of bronchiolitis obliterans syndrome, the LPAR1 antagonist AM095 or an ENPP2 inhibitor tool compound decreased fibrosis and airway wall thickness in the lung compared with vehicle. Next steps could include testing the inhibitors in additional models of bronchiolitis obliterans syndrome...