Lay Summary

Proposal No.  IBD-0021
Principal Investigator: Hudson Freeze, Ph.D.
Applicant Organization:  The Burnham Institute (La Jolla, California, U.S.A.)
Project Title:  An anti-glycan antibody (mAbGB3.1) as a novel therapy for Crohn's disease and ulcerative colitis
Period of Award:  August 1, 2002 - March 31, 2005

How ulcerative colitis and Crohn’s disease arise is not understood.  If we knew the mechanisms in detail, treatments that block one or more of the steps along the way towards inflammatory bowel disease (IBD) might be used as therapies.  Our group studies sugar chains on proteins.  These are not nutritional elements, rather these sugar chains affect the way proteins behave by themselves, bind each other, or send signals inside the cells.

We discovered a novel kind of sugar chain and found that it promotes the binding of two proteins whose interaction leads to IBD in mice.  We do not know the precise structure of the sugar chains, but we made an antibody against them with the idea that the antibody would bind to the sugar chains and block the two proteins from binding to each other.  Injecting this antibody into mice prevents the development of IBD-like disease.

We want to expand that work to include several different types of mouse models of IBD.  No single mouse model is perfect, so that several different ones are needed to get reliable information.  The dose and timing of antibody administration needs to be determined, and perhaps most importantly, we want to know if the antibody can reverse the disease in mice once they have shown moderate or severe disease.  If it does, we will need to know how fast it works and how much antibody is needed.  We will use various pathological and molecular markers to monitor health of the mice during the experiments.  The goal is to see whether our promising short-term results stand the test of time.  If they do, and do not cause serious side effects, the antibody may be a therapeutic tool for patients, since humans also have these kinds of sugar chains.

Ultimately, we also want to understand how these sugar chains influence IBD.  The study of sugar chains and their functions is just now becoming appreciated, spawning the new field of glycobiology.  Other well-established sugar chains are involved in inflammation and development of cancer.  Our new type of sugar chain appears to be important in IBD.