Inflammatory bowel disease: new therapies from antisense oligonucleotides

Marafini I1, Monteleone G1. Ann Med. 2018 Jun 16:1-22. doi: 10.1080/07853890.2018.1490025. [Epub ahead of print]

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1 a Department of Systems Medicine , University of Rome Tor Vergata , Italy.


Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract encompassing two main clinical entities: Crohn's disease (CD) and ulcerative colitis (UC). These disorders are characterized by various grades of tissue damage and development of local complications and extra-intestinal manifestations. The cause of IBD remains unknown but accumulating evidence indicates that both CD and UC arise in genetically-predisposed individuals as a result of the action of multiple environmental factors, which ultimately trigger excessive and poorly-controlled immune response against antigens of the luminal flora. In spite of this realization, a full understanding of IBD pathogenesis is still out of reach and, consequently, treatment is far from optimal. However, in recent years, several pathways of intestinal damage have been delineated and the improved knowledge has contributed to the development of new therapies. Various approaches have been used to either inhibit the expression and/or function of inflammatory molecules or enhance counter-regulatory mechanisms. This review summarizes the available pre-clinical and clinical data for antisense oligonucleotides and oligonucleotides to provide a comprehensive understanding of the rationale and mechanism of action of these compounds in IBD.

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