A New Small Molecule For Treating Inflammation and Chorioretinal Neovascularization in Relapsing-Remitting and Chronic Experimental Autoimmune XXXX .

@entity7940 @entity3692 @entity18295 @entity13358 @entity2295 @entity1596 @entity16308 @entity6519 @entity35 @entity6667 @entity792
PURPOSE: We investigated the effect of PP-001, a new small molecule inhibitor of dihydro-orotate dehydrogenase in two experimental @entity35 experimental @entity792 (EAU) models: a spontaneously relapsing-remitting model and a monophasic/chronic disease model that results in late @entity6519 . Both of the diseases are induced by immunization with autoantigen peptides. METHODS: Prevention was tested using daily oral applications of PP-001 after immunization with the @entity18295 peptide PDSAg (for induction of monophasic @entity1596 ) or the interphotoreceptor retinoid-binding protein peptide R14 (for induction of spontaneously relapsing-remitting EAU). Treatment to inhibit relapses and @entity2295 was tested using PP-001 daily after the first attack of R14-induced or after onset of PDSAg-induced EAU. @entity1596 was graded clinically and histologically. The effect of PP-001 on cytokine secretion and proliferation was evaluated using @entity35 T-cell lines. RESULTS: Preventive feeding of PP-001 abrogated both types of EAU. Starting treatment after the resolution of the first attack led to a significant reduction of the number and intensity of relapses in R14-induced EAU. PP-001-treatment initiated after onset or after peak of PDSAg-induced EAU significantly reduced @entity2295 (as determined by histology). Proliferation of antigen-specific T-cell lines and secretion of IFN-y, @entity7940 , @entity13358 , @entity16308 , and @entity6667 were efficiently suppressed by PP-001. CONCLUSIONS: We investigated a new dihydroorotate dehydrogenase inhibitor as treatment for primary and recurrent disease in relapsing-remitting and chronic @entity35 models of experimental @entity792 . The small molecule compound PP-001 suppressed proliferation and cytokine secretion of autoreactive T cells (i.e., @entity3692 , @entity7940 , and @entity6667 ) and @entity6519 in chronic EAU.
