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.

Marafini, I., Di Fusco, D., Calabrese, E., Sedda, S., Pallone, F., & Monteleone, G. (2015). Antisense approach to inflammatory bowel disease: Prospects and challenges. DRUGS, 75(7), 723-730 [10.1007/s40265-015-0391-0].

Antisense approach to inflammatory bowel disease: Prospects and challenges

CALABRESE, EMMA;PALLONE, FRANCESCO;MONTELEONE, GIOVANNI
2015

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/12 - Gastroenterologia
English
Animals; Clinical Trials as Topic; DNA; Humans; Inflammatory Bowel Diseases; Oligonucleotides; Oligonucleotides, Antisense; Phosphorothioate Oligonucleotides; Pharmacology (medical); Medicine (all)
http://rd.springer.com/journal/40265
Marafini, I., Di Fusco, D., Calabrese, E., Sedda, S., Pallone, F., & Monteleone, G. (2015). Antisense approach to inflammatory bowel disease: Prospects and challenges. DRUGS, 75(7), 723-730 [10.1007/s40265-015-0391-0].
Marafini, I; Di Fusco, D; Calabrese, E; Sedda, S; Pallone, F; Monteleone, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/154087
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