Crohn’s disease (CD) and ulcerative colitis (UC), two chronic and relapsing inflammatory bowel diseases
(IBD), are supposed to develop in genetically-predisposed individuals as a result of an excessive immune mucosal response
directed against normal components of the gut microbiota. There is also evidence that defects in counter-regulatory
mechanisms play a major role in the pathogenesis of IBD. One such a defect involves TGF-β1, a cytokine produced by
multiple cells types and able to inhibit pathogenic responses in the gut. In both CD and UC, TGF-β1 is highly produced
but unable to signal through the TGF-β receptor-associated Smad pathway and suppress production of inflammatory
molecules. Abrogation of TGF-β1 activity has been related to Smad7, an intracellular protein that binds to TGF-β receptor
and inhibits TGF-β1-driven Smad-dependent signalling. Indeed, silencing of Smad7 with a specific antisense oligonucleotide
restores TGF-β1/Smad signalling, thereby down-regulating inflammatory cytokine production and ameliorating experimental
colitis in mice. Altogether these observations led to the development of an oral pharmaceutical compound containing
the specific Smad7 antisense oligonucleotide (herein termed GED0301), which seems to be safe and well tolerated
in CD patients. In this article we summarize the data supporting the pathogenic role of Smad7 in IBD and discuss the recent
results of the use of GED0301 in CD.
Keywords: Smad7, colitis, antisense oligonucleotide, Crohn’s disease, ulcerative colitis.
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