Targeting MK2 for Crohn's Disease

Crohn's disease is a debilitating disease that causes significant colon damage and lacks a cure. Current treatment approaches are only managing the disease and often fail, thus new treatments are badly needed to improve the quality of life for people with this disease. In this study, we propose that the intracellular signaling pathway known as MK2 is a potential target to limit damaging inflammation and efficiently improve current treatment approaches. The small-molecule drug that specifically block this pathway has been recently developed against MK2 due to its critical involvement in the chronic inflammatory lung diseases. However, MK2 has been overlooked in the field of Crohn's disease research. Using human tissue derived from active disease, we initially demonstrated that MK2 is hyperactive in Crohn's disease. We were also able to identify two major cells types (known as myo-/fibroblasts and CD4+ T cells) that show increase in MK2 activity. Finally, our initial data suggests that blocking this signaling in the above cells in culture and in a mouse models of Crohn's disease dramatically decreases disease-specific inflammation and significantly improves symptoms and distress of the disease. Inflammation-induced fibrosis in Crohn's disease is another major complication to which no treatment, besides surgical intervention, is currently available. Our initial data suggest that targeting MK2 is likely to be a promising way to reduce/treat the devastating complications of Crohn's disease. Thus, we propose to test if blocking the MK2 is a new treatment approach to inhibit damaging responses and could be a new treatment target for Crohn's disease.We expect to identify a new mechanism of damaging immune responses in Crohn's disease by (1) stromal mesenchymal cells, (2) CD4+ T cells, and (3) to provide the preclinical work necessary to bring a new treatment approach to help patients with ongoing symptoms of the disease. This study is led by a dual Principal Investigator team with the likelihood of establishing a new treatment approach if supported for these studies. The overall impact could help a significant amount of the military and Veteran population.