Grants and Contracts Details
Description
Lay Abstract:
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 drugs that specifically block this pathway has been recently
developed against MK2 due to its critical involvement in the chronic inflammatory lung diseases. However,
MK2 was completely overlooked in the field of Crohn’s Diseases. Using human tissue derived from active
disease we initially demonstrated that MK2 is hyperactive in Crohn’s Disease. We were also been 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 the
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) provide the pre-clinical work necessary to bring a new treatment
approach to help patients with ongoing symptoms of the disease. This study is led by a Dual-PI team with the
likelihood of establishing a new treatment approach if supported for these studies. The overall impact could
help a significant amount of military and veteran population.
Status | Active |
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Effective start/end date | 6/1/23 → 5/31/26 |
Funding
- Department of Defense: $1,688,887.00
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