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A new treatment for Crohn’s disease is being tested. This method involves targeting of the SMAD7 protein using the antisense drug, mongersen.

Crohn’s disease is one of the two main types of inflammatory bowel disease. Crohn’s disease is characterised by inflammation of the GI tract, usually the lower portion of the small bowel and the colon. This inflammation can result in impaired ability to digest and absorb nutrients from food, abdominal pain, cramping, gas, bloating, fatigue, diarrhea, and loss of appetite.

Research has focused on drugs that target the inflammatory pathways involved in Crohn’s disease. A recent drug has been designed to target the SMAD7 protein. This protein is increased in Crohn’s disease, and causes a reduction in TGF B1, which is involved in immunosuppressive pathways.

Mongersen (GED0301) is an antisense oligonucleotide molecule (a complementary sequence of DNA) that attaches to the SMAD7 mRNA, a precursor to the SMAD7 protein, resulting in its destruction within the cell and reduced levels of SMAD7 protein production.


Oligonucleotide Mechanism Image                 How Does an Antisense Oligonucleotide Work?

An antisense oligonucleotide is a complementary strand of mRNA that

binds to an mRNA molecule in the cell before it becomes a protein.

When the oligonucleotide is attached to the mRNA, it prevents the

production of the specific protein.

(Source: Gene Therapy for Gynecologic Cancer)


Studies of mongersen in mice have demonstrated a reduction in SMAD7 production, resulting in prevention or reduction of Crohn’s disease-like colitis. The aim of the present study was to determine safety and effectiveness of mongersen in patients with Crohn’s disease.

The phase 2 trial included participants who were aged between 18-75 years old, with moderate-severe Crohn’s disease, who were steroid-dependent, or glucocorticoid resistant, according to the guidelines of the European Crohn’s and Colitis Organization. Patients were given either 10, 40, or 160mg of mongersen, or placebo, daily for 2 weeks. Participants were assessed on days 15, 28, and 84.

Clinical remission was seen for 65% of patients in the 160mg group, 55% of patients in the 40mg group, and 12% in the 10mg group, compared with 10% in the placebo group. A clinical response at day 28 was greater in the 160mg group (72%), 40-mg group (58%), and 10-mg group (37%) than in the placebo group (17%).

Overall the results demonstrated a clinical benefit of mongersen in patients with active Crohn’s disease. This effect was highest in the higher dose groups of 160mg and 40mg per day.

The researchers suggest that future study should focus on comparison of mongersen with currently available Crohn’s treatments, in addition to further study into the optimal dosage and schedule.


Crohn’s and Colitis Canada “What are Crohn’s and Colitis” Available from: Last Accessed March 25, 2015.

Huh, WK, Barnes, MN. Chapter 64 “Gene Therapy for Gynecologic Cancer”

Monteleone, G, Neurath, MF, Ardizzone, S, Di Sabatino, A, Fantini, MC, Castiglione, F, Scribano, ML, Armuzzi, A, Caprioli, F, Sturniolo, GC, Rogai, F, Vecchi, M, Atreya, R, Bossa, F, Onali, S, Fichera, M, Corazza, GR, Biancone, L, Savarino, V, Pica, R, Orlando, A, Pallone, F. “Mongersen, an Oral SMAD7 Antisense Oligonucleotide, and Crohn’s Disease” New England Journal of Medicine, 2015; 372:1104-1113 March 19, 2015 DOI: 10.1056/NEJMoa1407250

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Written by Deborah Tallarigo,  PhD

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