Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease

The New England Journal of Medicine
Giovanni MonteleoneFrancesco Pallone

Abstract

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. In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the...Continue Reading

References

Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A B KulkarniS Karlsson
Jun 1, 1996·The Journal of Experimental Medicine·M F NeurathW Strober
Apr 21, 2001·Gastroenterology·S SchreiberUNKNOWN German ICAM-1 Study Group
Aug 24, 2001·The Journal of Clinical Investigation·G MonteleoneT T MacDonald
Oct 13, 2001·The New England Journal of Medicine·J KeaneM M Braun
Nov 6, 2003·The Journal of Biological Chemistry·Giovanni MonteleoneThomas T MacDonald
Sep 7, 2005·Gastroenterology·Stefan SchreiberUNKNOWN CDP870 Crohn's Disease Study Group
Feb 25, 2006·Scandinavian Journal of Gastroenterology·Timothy H J FlorinGraham L Radford-Smith
Apr 17, 2007·Digestive Diseases and Sciences·Alexander D Rodgers, Adrian G Cummins
Dec 23, 2008·Mucosal Immunology·G MonteleoneT T MacDonald
Aug 21, 2010·Inflammatory Bowel Diseases·Laurent Peyrin-BirouletWilliam J Sandborn
Dec 3, 2010·Journal of Crohn's & Colitis·Gert Van AsscheUNKNOWN European Crohn's and Colitis Organisation (ECCO)
Mar 17, 2011·The American Journal of Gastroenterology·Alexander C FordPaul Moayyedi
Jan 19, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Giovanni MonteleoneFrancesco Pallone
Oct 16, 2012·Cellular Signalling·Rohan SamarakoonPaul J Higgins
Mar 26, 2013·PloS One·Satish KeshavUNKNOWN Prospective Randomized Oral-Therapy Evaluation in Crohn’s Disease Trial-1 PROTECT-1 Study Group
Jul 23, 2013·Journal of Crohn's & Colitis·F MagroUNKNOWN European Crohn's and Colitis Organisation (ECCO)
Aug 24, 2013·The New England Journal of Medicine·William J SandbornUNKNOWN GEMINI 2 Study Group

❮ Previous
Next ❯

Citations

Jan 15, 2016·Expert Review of Gastroenterology & Hepatology·Federica FurfaroSilvio Danese
Nov 13, 2015·Expert Review of Clinical Immunology·Sebastian Zundler, Markus F Neurath
Jan 15, 2016·Cytokine & Growth Factor Reviews·Lovorka GrgurevicSlobodan Vukicevic
Jan 8, 2016·Journal of the American Chemical Society·Mark W TibbittRobert Langer
Sep 30, 2015·The Journal of Infectious Diseases·Andre KublerWilliam R Bishai
Jan 29, 2016·Journal of Crohn's & Colitis·Ivan MonteleoneGiovanni Monteleone
Feb 4, 2016·International Journal of Inflammation·Canan AlkimIlker Sen
Dec 3, 2015·Nature Reviews. Gastroenterology & Hepatology·Heitor S P de Souza, Claudio Fiocchi
Aug 19, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gerhard Rogler
Mar 24, 2016·Ocular Immunology and Inflammation·James T RosenbaumMark Asquith
Mar 12, 2016·Expert Opinion on Investigational Drugs·Ole Haagen NielsenMehmet Coskun
Apr 1, 2016·Clinical and Translational Gastroenterology·Maisa Abdalla, Shehzad Z Sheikh
Jun 18, 2015·The New England Journal of Medicine·Giovanni Monteleone, Francesco Pallone
Apr 1, 2015·Nature Reviews. Gastroenterology & Hepatology·Katrina Ray
Apr 26, 2015·Drugs·Irene MarafiniGiovanni Monteleone
Mar 19, 2015·The New England Journal of Medicine·Severine Vermeire
May 21, 2016·Frontiers in Immunology·Michelle A SugimotoMauro M Teixeira
May 18, 2016·Current Gastroenterology Reports·Aranzazu Jauregui Amezaga, Gert Van Assche
Apr 27, 2016·Journal of Crohn's & Colitis·Imke AtreyaMarkus F Neurath
Feb 24, 2016·Expert Review of Clinical Immunology·Patrick B Allen, Laurent Peyrin-Biroulet
May 18, 2016·Journal of Neurogastroenterology and Motility·Sutheera Ratanasirintrawoot, Nipan Israsena
Jul 16, 2016·Clinical and Translational Gastroenterology·Moira ParoniFlavio Caprioli
Jul 28, 2016·Expert Review of Gastroenterology & Hepatology·Tawnya Hansen, Laura E Targownik
Jul 28, 2016·Current Gastroenterology Reports·Parambir S Dulai, William J Sandborn
Sep 20, 2016·Current Rheumatology Reports·James T Rosenbaum, Mark J Asquith
Oct 1, 2016·Cell Death and Differentiation·Maria Paola ParonettoClaudio Sette
Oct 13, 2016·Scientific Reports·Shih-Yao ChenChrong-Reen Wang
Nov 11, 2016·Journal of Gastroenterology·Heyson Chi-Hey Chan, Siew Chien Ng
Jan 31, 2017·Expert Opinion on Biological Therapy·Simon Hirschmann, Markus F Neurath
Feb 2, 2017·Nature Reviews. Gastroenterology & Hepatology·Markus F Neurath
Jan 16, 2017·Gastroenterology·Carl M SchoellhammerGiovanni Traverso
Mar 11, 2017·Expert Opinion on Therapeutic Targets·Tommaso GabbaniVito Annese
Dec 7, 2016·Cold Spring Harbor Perspectives in Biology·Keiji Miyazawa, Kohei Miyazono
Mar 28, 2017·Epigenomics·Richard Kellermayer
Apr 14, 2017·Clinical and Translational Gastroenterology·Oriana M DamasJacob L McCauley
Dec 16, 2016·Parasite Immunology·D E Elliott, J V Weinstock
Dec 5, 2016·Lancet·Joana TorresLaurent Peyrin-Biroulet
Mar 15, 2016·Journal of Pediatric Gastroenterology and Nutrition·Sana SyedChristopher Duggan
Apr 14, 2017·Current Opinion in Gastroenterology·Heitor S P de Souza
Apr 14, 2017·The Lancet. Gastroenterology & Hepatology·Maša Umićević MirkovIsabelle Cleynen
Dec 7, 2016·Life Sciences·Eduardo Esteban-ZuberoRussel J Reiter
Dec 6, 2016·Trends in Pharmacological Sciences·Mehmet CoskunOle Haagen Nielsen
Mar 7, 2017·Immune Network·Duk Hwan Kim, Jae Hee Cheon
Jul 2, 2016·Therapeutic Advances in Gastroenterology·Sandro ArdizzoneGiovanni Monteleone
Sep 22, 2017·International Journal of Molecular Sciences·Grainne HolleranFranco Scaldaferri

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Related Papers

The New England Journal of Medicine
Gulen HatemiYusuf Yazici
The New England Journal of Medicine
Martin SchlumbergerSteven I Sherman
The New England Journal of Medicine
Jennifer G RobinsonODYSSEY LONG TERM Investigators
Molecular Therapy : the Journal of the American Society of Gene Therapy
Giovanni MonteleoneFrancesco Pallone
© 2021 Meta ULC. All rights reserved