Clinical development of the toll-like receptor 9 agonist DIMS0150 in chronic active ulcerative colitis patients
Ulcerative colitis (UC) is an immune-mediated condition characterized by a continuous mucosal inflammation of the colon, which might be caused from the dysregulated balance between commensal enteric flora and the gut-associated immune system. A proportion of patients do not respond to available therapies becoming treatment refractory and requiring surgical intervention and therefore novel treatment strategies are needed (1-3).
One of the ways that host discerns foreign from self-antigen is through pattern recognition receptors (PRRs), which recognize specific molecular patterns of pathogens. One group of PRRs consists of Toll-like receptors (TLRs) with variable specificities for sensing microbial products. One of these receptors, TLR-9, recognizes exclusively bacterial DNA and has over the years received growing interest as a potential target for therapeutic intervention in the treatment of UC. It could be shown that TLR-9 activation prevents development of mucosal inflammation and promotes wound healing in several models of experimental colitis (4-6).
DIMS0150 is a fu ...