Project

Clarifying the Molecular Mechanisms and Creating a Treatment Strategy for Inflammatory Bowel Disease

Summary

Inflammatory bowel disease (IBD), broadly classified into ulcerative colitis (UC) and Crohn’s disease (CD), causes chronic inflammation of the mucous membrane of the large and small intestines. The origin of this digestive system disease is of unclear origin and it is classified as an intractable disease by the Ministry of Health, Labour and Welfare. IBD is characterized by abnormal white blood cell activity in the large intestine mucous membrane, and long-term inflammation during repeated remission and relapse is a cause of colon cancer. In Japan, approximately 160,000 people suffer from UC, and 40,000 suffer from CD, which is a large number among intractable diseases. Worldwide, incidence is highest among people in their 20s to 30s. The number of people suffering from IBD is over 5 million, with a morbidity rate that is remarkable in developed countries and it is feared that incidence will rapidly increase in developing countries along with westernization of diet and urbanization.

 

In this research, we used protein interaction visualization markers developed at the Life Science Center for Survival Dynamics, University of Tsukuba, to find that the interaction between intracellular protein calreticulin (CRT) and white blood cell adhesion molecule integrin (ITGA) increased at the site of UC inflammation. Additionally, we discovered a new mechanism that suppresses adhesion and permeation of white blood cells with an analog of low molecular weight therapeutic agents created by Eisai and under trials at EA Pharma that blocks CRT-ITGA. Furthermore, transcriptome analysis revealed this analog had a remarkable anti-inflammatory effect when orally administered to IBD model mice and it programmed genetic information for the process of “normal-inflammation-improvement”. (Nature Commun. 2018, doi:10.1038/s41467-018-04420-4)

 

This low molecular weight compound is currently in phase II trials as an IBD therapeutic agent candidate with oral efficacy. In the future, we will use the CRT-ITGA interaction detection method as a biomarker in clinical development to create a new treatment strategy (Supported by JST’s Newly Extended Technology Transfer Program, NexTEP: Treatment of inflammatory bowel disease with low molecular weight compounds and biomarkers, J13-06).

*University of Tsukuba press release:http://www.tsukuba.ac.jp/attention-research/p201805251400.html
*NexTEP:https://www.jst.go.jp/jitsuyoka/topics/saitaku_201403.html

Company

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance

Main member