Rho-kinase (ROCK) is a critical mediator of both biomechanical (tissue stiffness) and biochemical (TGF-b mediated) pathways involved in the dysregulated activation of myofibroblasts, the cells thought to underlie the pathogeneisis of fibrotic disease. Aberrant expression and activation of ROCK results in sustained presence of activated myofibroblasts and excessive extracelluar matrix production, leading to tissue fibrosis. ROCK exists as two highly related isoforms, ROCK1 and ROCK2. Lycera is currently progressing potent, highly-specific inhibitors of the ROCK2 isoform, which has recently been demonstrated to inhibit the production of pathogenic cytokine IL-17 in immune cells. Lycera’s ROCK inhibitors are currently being investigated in pre-clinical models of fibrosis.
Publications for ROCK Inhibitors
2016 European Crohn’s and Colitis Organization (Poster): Anti-fibrotic therapy for Crohn’s Disease: In vitro proof of concept with a selective ROCK2 inhibitor, LYC-53976, in the treatment of human intestinal myofibroblasts in stiffness and transforming growth factor β model. E. Rodansky, X. Liu, L. A. Johnson, K. Demock, A. J. Celeste, L. L. Carter, P. D. R. Higgins