BioCentury
ARTICLE | Distillery Therapeutics

Transplant

January 23, 2018 9:12 PM UTC

Patient sample and mouse studies suggest inhibiting P2RX7 could help treat transplant rejection. In blood samples from liver transplant patients, monocyte levels of P2RX7 were higher in patients who rejected their transplants than in patients who did not. In a mouse model of skin transplant, systemic knockout of P2XR7 decreased epithelial hyperplasia, inflammatory cell infiltration and necrosis in the graft, serum levels of anti-graft antibodies and scores of graft rejection severity compared with normal expression. Also in the model, a tool compound P2XR7 antagonist decreased epithelial thickness, inflammatory cell infiltration and necrosis in the graft, and serum levels of proinflammatory cytokines, compared with vehicle. Next steps include testing undisclosed inhibitors of P2RX7 and its downstream pathway in transplant rejection patients.

Evotec AG and Zhejiang Conba Pharmaceutical Co. Ltd. have EVT401, an oral small molecule P2X7 receptor antagonist, in Phase II testing to treat inflammation and Phase I testing to treat rheumatoid arthritis...