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01.05.2015 | Leading Article

Antisense Approach to Inflammatory Bowel Disease: Prospects and Challenges

verfasst von: Irene Marafini, Davide Di Fusco, Emma Calabrese, Silvia Sedda, Francesco Pallone, Giovanni Monteleone

Erschienen in: Drugs | Ausgabe 7/2015

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Abstract

Despite the great success of anti-tumour necrosis factor-based therapies, the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) still remains a challenge for clinicians, as these drugs are not effective in all patients, their efficacy may wane with time, and their use can increase the risk of adverse events and be associated with the development of new immune-mediated diseases. Therefore, new therapeutic targets are currently being investigated both in pre-clinical studies and in clinical trials. Among the technologies used to build new therapeutic compounds, the antisense oligonucleotide (ASO) approach is slowly gaining space in the field of inflammatory bowel diseases (IBDs), and three ASOs have been investigated in clinical trials. Systemic administration of alicaforsen targeting intercellular adhesion molecule-1, a protein involved in the recruitment of leukocytes to inflamed intestine, was not effective in CD, even though the same compound was of benefit when given as an enema to UC patients. DIMS0150, targeting nuclear factor (NF) κB-p65, a transcription factor that promotes pro-inflammatory responses, was very promising in pre-clinical studies and is currently being tested in clinical trials. Oral mongersen, targeting Smad7, an intracellular protein that inhibits transforming growth factor (TGF)-β1 activity, was safe and well tolerated by CD patients, and the results of a phase II clinical trial showed the efficacy of the drug in inducing clinical remission in patients with active disease. In this leading article, we review the rationale and the clinical data available regarding these three agents, and we discuss the challenge of using ASOs in IBD.

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Titel: Antisense Approach to Inflammatory Bowel Disease: Prospects and Challenges
verfasst von: Irene Marafini
Davide Di Fusco
Emma Calabrese
Silvia Sedda
Francesco Pallone
Giovanni Monteleone
Publikationsdatum: 01.05.2015
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 7/2015
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-015-0391-0

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Antisense Approach to Inflammatory Bowel Disease: Prospects and Challenges

Abstract

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

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