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A new biologic approach for treating inflammatory bowel diseases (IBD)

Inflammatory bowel disease (IBD), mainly ulcerative colitis and Crohn’s disease, are chronic and debilitating diseases that affect 1 in every 150 Canadians and an increasing number of children. The chronic inflammation underlying IBD might result from an abnormal activation of the intestine mucosal immunity stimulated by danger signals or damage associated molecular pattern molecules.

The laboratory of Prof Sévigny studies the roles and functions of extracellular nucleotides in intestine mucosal inflammation. Once released in the intestine, nucleotides (ATP, ADP, and UDP) can activate P2Y or P2X receptors and provoke an inflammatory stress. P2 receptor activation is terminated by ectonucleotidases, such as NTPDases, enzymes that hydrolyze nucleotides to yield adenosine, a potent anti-inflammatory agent.

The team of Prof Sévigny has shown that NTPDase8 is the major ectonucleotidase expressed at the apical surface of the mouse intestinal epithelium, and recently demonstrated that the intra-rectal administration of apyrase, an enzyme mimicking the action of NTPDase8, can prevent inflammation in the dextran sulfate (DSS) animal model of induced colitis, a model applicable to human diseases.

References

  • Sévigny J and M Salem (2018). Treatment of inflammatory bowel disease with nucleoside triphosphate disphosphorhydrolase, P2Y2 antagonist and/or P2Y6 antagonist. WO2018058246A1, CA3037779A1. Assignee: Université Laval.

  • Pelletier J, M Salem, J Lecka, M Fausther, F Bigonnesse, and J Sévigny (2017). Generation and characterization of specific antibodies to the murine and human ectonucleotidase NTPDase8. Front Pharmacol 8: 115.

  • Salem M, A Tremblay, J Pelletier, B Robaye, and J Sévigny (2018). P2Y6 receptors regulate CXCL10 expression and secretion in mouse intestinal epithelial cells. Front Pharmacol 9: 149.

  • Crohn's and Colitis Canada (2019). Discovering novel treatments. Available at: https://crohnsandcolitis.ca/Research/Funded-research/Discovering-Novel-Treatments.

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Opportunities

NTPDase8 might provide a "first-in-class" biologic solution for treating inflammatory bowel diseases.

SOVAR and Université Laval seek a partner for co-development of an enteric formulation of NTPDase8 or commercialization of this technology.

Availables resources

The laboratory of Prof Sévigny is fully capable of in vitro and in vivo evaluation of compounds in cellular and animal models of IBD.