Small molecule, big hope Innovating inflammatory bowel disease therapy

Imagine living with a chronic inflammation of all or part of your digestive tract. Add some symptoms, such as severe diarrhea, pain, fatigue, and weight loss. Medication? Forget it. There is no cure to this condition. It doesn’t sound very encouraging, does it?

The unfortunate part of this story is that this disease exists and it is called inflammatory bowel disease (IBD). IBD primarily includes ulcerative colitis and Crohn’s disease, which can lead to debilitating and sometimes life-threatening complications. Luckily, there are some researchers working very hard to find drugs and therapies that might help to alleviate the symptoms and hopefully lead to the cure of such complicated disease.

Mohammad Rabbi, a PhD. candidate in the department of immunology and internal medicine, is one such researcher who is working under the supervision of professor Jean-Eric Ghia.

“IBD is thought to arise secondary to a genetically determined susceptibility to inflammation triggered by unknown environmental factors,” Ghia explains in his U of M research profile.

“The most common course of disease is one of recurrent relapses. The disease and relapses include behavioural, neuroimmune, endocrine and enteric neuronal dysregulation, all of which may be interconnected.”

Rabbi has been studying how a small peptide can affect monocytes, which seems to have antimicrobial activity.

“Mucosal inflammation in inflammatory bowel disease patients is characterized by an alteration of Chromogranin A (CgA) production. CgA is recognized as a neuroendocrine tumor marker present in the enterochromaffin cells (EC) and can serve as a prohormone for shorter bioactive fragments,” Rabbi said.

EC cells are found in the epithelia tissue of the digestive tract and the respiratory tract. They are distributed widely in the epithelium of the stomach,small bowel, and colon.

“A certain portion of CgA is highly conserved throughout evolution suggesting that it has important biological functions,” said Rabbi.

Two peptides (short chains of amino acid) derived from CgA, catestatin and its short version called cateslytin, are known to have antimicrobial and chemotactic properties.

To explain the role of the peptides that he has been studying, Rabbi highlighted some aspects of the disease:

“Inflammatory bowel diseases are chronic, relapsing intestinal disorders of complex pathogenesis … including Crohn’s disease (CD) and ulcerative colitis (UC). IBD is the most common and serious chronic inflammatory condition of the gastrointestinal tract.”

Approximately 15 out of 100,000 Canadians are affected by each disease, according to Rabbi.

“Current treatments for IBD address the symptoms and are not curative, and they have potentially serious side effects. Thus, new, effective and safer therapies are required,” said Rabbi.

“As the cause of IBD is not well understood, the elucidation of new regulatory pathways implicated in the IBD’s pathogenesis will have great potential in the development of new therapeutic strategies” Rabbi.

Rabbi’s research is highly novel, and they expect it to lead to new diagnostic markers in IBD and to development of new antibacterial peptides.

The vision of Rabbi and his supervisor is to develop a better understanding of the pathogenesis of IBD and, in so doing, to develop new treatment paradigms that are both safer and more effective than current treatment options.

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