For auto-immune diseases, the question is always whether suppressing over-activity will cause more disease than it prevents. In this case, the pathway affects

For auto-immune diseases, the question is always whether suppressing over-activity will cause more disease than it prevents. In this case, the pathway affects macrophages, leucocyte activation and migration, and production of 3 inter-leukin's and other cytokines -- which doesn't offer much hope at avoiding off-target effects. As they mention, this gene is shared as far back as other proto-humans, so it's likely essential. And they didn't really need this finding to consider targeting (toxic) MEK at macrophages using antibodies, particularly since GI drugs can be made relatively non-absorbable, further reducing off-target effects. But since these are chronic diseases with wide variations between patients of severity and tissue involvement, and since macrophage activity is relatively acute, the narrow therapeutic range of a MEK-based drug is far from ideal: too much opportunity for overdose. So I hope this stimulates more investigation of the ETS2-mediated pathways, but I don't hold out much hope for a MEK + Ab drug for IBD.