Crohn’s disease–related inflammation is characterized by reduced activity of the immunosuppressive cytokine

Crohn’s disease–related inflammation is characterized by reduced activity of the

immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high

levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.

Crohn’s disease is a chronic inflammatory illness that primarily affects the

terminal ileum and right colon. Crohn’s disease–related inflammation is segmental and transmural, leading to various degrees of tissue damage.


At disease onset, most patients have inflammatory lesions, which become predominantly strictures or penetrating lesions over time.


Mucosal healing can be promoted with the use of immunosuppressive drugs and anti–tumor necrosis factor α (TNF-α) antibodies; however, more

than one third of patients do not have a response to these therapies.


The efficacy of these drugs may also diminish over time, and they can increase a patient’s risk of opportunistic infections and cancer.

Therefore, there is a need for novel drugs that target the major inflammatory pathways in Crohn’s disease.


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