Ophthalmic disease

Patient sample and mouse studies suggest inhibiting mast cell degranulation, TPSB2 or MCP-1-CCR2 signaling could help treat retinopathy of prematurity (ROP). In plasma samples from preterm neonatal infants who developed ROP, levels of the mast cell activation marker TPSB2 were higher than in preterm neonatal infants who did not develop the disease. In a mouse model of ROP, a mast cell degranulation inhibitor tool compound, a TPSB2 inhibitor tool compound or an anti-TPSB2 antibody decreased pathological retinal neovascularization compared with vehicle or an isotype control antibody. Also in the model, intravitreous injection of siRNA targeting the pro-angiogenic factor MCP-1 or systemic knockout of the MCP-1 receptor CCR2 decreased pathological retinal neovascularization compared with normal MCP-1 and CCR2 expression. Next steps include testing undisclosed inhibitors of mast cell degranulation in preterm neonatal patients at risk for retinal neovascularization.

ChemoCentryx Inc. has CCX140, an inhibitor of CCR2, in Phase II testing to treat diabetic nephropathy and in preclinical testing to treat nephropathy...