Researchers Replicate Celiac Disease in Mice

By Dr. Valerie Abadie
Assistant Professor, Department of Microbiology, University of Montreal

 

Canadian scientists have figured out how to replicate celiac in mice, which could lead to breakthroughs in new treatments.

Celiac disease (CD) is highly prevalent in North America, with around one percent of the Canadian population affected by the disease. The classical pathological changes of CD in the small bowel encompass an increased number of intraepithelial lymphocytes, the presence of autoantibodies, and a destruction of the lining of the small intestine (called villous atrophy). The only effective treatment currently available for CD is a lifelong gluten-free diet (GFD), yet persistent symptoms and intestinal tissue damage are common among celiac patients that adhere to a GFD.

Non-dietary therapies that would improve patient health and alleviate the social and personal constraints associated with following a GFD are under investigation. However, the development of new therapies has proven challenging because of our incomplete understanding of the mechanisms responsible for damaging the intestinal tissue and the lack of a disease-relevant animal models.

Several animal models of gluten-sensitive disorders have substantially contributed to a better understanding of how gluten intolerance can arise and cause disease, yet none of them represent a suitable mouse model for preclinical validation of new celiac drug targets as they do not display intestinal tissue destruction upon gluten ingestion as seen in active CD patients.

For the past years, with the support of the J.A. Campbell Research Award, the laboratory of Dr. Abadie at the University of Montreal and the CHU Sainte-Justine Research Center in collaboration with the laboratory of Dr. Jabri at the University of Chicago has worked extensively on the characterization of a novel mouse model that develops all the features of CD upon gluten ingestion including the development of villous atrophy.

Following oral gluten administration, the development of anti-gluten immune responses characterized by the expansion of cytotoxic lymphocytes and the development of antibodies against gluten, as well as CD-associated histological abnormalities were monitored and confirmed that this model develops a disease that closely resembles human CD.

In addition, this work confirmed that the induction of CD-like pathology requires the predisposing genetic factor HLA-DQ8 as in humans. This new mouse model is likely to revolutionize research in CD by allowing studying the complex immune mechanisms that lead to villous atrophy. Hence, it is currently used to take the first steps towards the mechanistic characterization of the immunological players involved in the development of villous atrophy in CD, and to better understand how intestinal immune responses towards gluten are deregulated in the context of CD. In particular, Dr. Abadie’s group is studying how B lymphocytes -specialized cells involved in the secretion of antibodies and autoantibodies- contribute to the pathogenesis of CD and whether autoantibodies against the enzyme tissue transglutaminase contribute to the development and/or the exacerbation of the disease. In addition of allowing to considerably gain some fundamental knowledge on CD pathogenesis, this long-awaited physiological animal model of CD represents an invaluable tool for the preclinical validation of new celiac drug targets and to test novel non-dietary therapies.

Donors to Match Celiac Research Fund

by Anne Wraggett, CCA President

At our National Conference in St. John’s last month, two CCA members offered to match all the donations up to $10,000 made to the CCA’s J. A. Campbell Research Fund between June 24 and August 31, 2016. That means that if you make a donation of $50, the research fund will grow by $150.

What does the CCA’s J. A. Campbell Research Fund do? It makes two awards each year: up to $25,000 to an established researcher and up to $5,000 to a young investigator (usually a graduate student working with a mentor). The research projects have to study something related to celiac disease, gluten sensitivity or the gluten-free diet. The projects frequently have a scientific or medical focus, but they can also focus on issues that affect the life of someone who must eat gluten free.

Applications are reviewed by the members of our Professional Advisory Council and the grants are making a BIG IMPACT! The CCA provided Dr. Elena Verdú with a small grant a few years ago and now she heads a research lab investigating host-microbial and dietary interactions in the context of celiac disease and gluten sensitivity at McMaster University in Hamilton Ontario.

With your help, and thanks to our two very generous matching donors, we can add an entire year of funding to the Campbell fund in just 6 weeks!! Help us reach that goal!

There are 3 ways to make your donation:

  1. Click here to make your donation online using the secure facilities of Canadahelps.org, OR
  2. Call the office toll free at 800-363-7296 to make a credit card donation, OR
  3. Mail your cheque to the national office today.

Canadian Celiac Association
5025 Orbitor Drive, Building 1, Suite 400
Mississauga, ON L4W 4Y5

Please identify your donation for CCA’s J. A. Campbell Research Fund on your cheque.

Thank you for your generous help with this project.

Anne Wraggett
President
CCA Board of Directors