New clinical research results were released in a recent publication of Gastroenterology, a journal of the American Gastroenterology Association. The study, conducted by leading gastroenterologists, examined the effects of the combination of the compounds hydroxyethyl methacrylate and styrene sulfonate, also called P(HEMA-co-SS). The results of the study revealed that P(HEMA-co-SS) reduces the immune system response in gluten-sensitized rodents and tissue samples taken from small intestinal biopsies of individuals with celiac disease.
To find out what this discovery means to people living with celiac disease, NFCA went right to the source and talked to the researchers about the implications of the study.
Q & A with Elena F. Verdu, MD, PhD of Farncombe Family Digestive Health Research Institute, McMaster University
Can you describe what hydroxyethyl methacrylate and styrene sulfonate are?
These are two subunits that form the gluten binder polymer chemical structure, and that ensure a good binding with the gliadin molecule. At a high acidity, as it occurs in the stomach, the gliadin molecule has positive charges. The subunit “SS” is negatively charged and thus has affinity for gliadin (what we call “electrostatic interactions”). Once in the small intestine, the HEMA subunit forms hydrogen bonds with gliadin, which is a “hydrophobic" protein (meaning it does not dissolve in water). This allows preferential binding of the polymer with gliadin, and not to other hydrophilic proteins in the gastrointestinal tract.
Can you explain P(HEMA-co-SS) reduces the immune response?
The polymer, now called BL-7010 and that is being developed pre-clinically as an adjuvant therapy in celiac disease by Bioline Rx, sequesters the gliadin molecule in the gastrointestinal tract. In doing so, the gliadin molecule is no longer accessible to the action of the digestive enzymes, which are the ones that break the gliadin molecule into small peptides that then induce an immune response in celiacs. Thus the polymer has two mechanisms of action, 1) it removes gliadin to prevent its contact with the intestinal lining, thereby excreting the complex BL-7010-gliadin in the feces, and 2) it protects gliadin from the action of the digestive enzymes thereby reducing the amount of toxic peptides produced.
How were these compounds identified as potential therapies for celiac disease?
BL-7010 was invented by Prof Jean-Cristophe Leroux, at the University of Montreal, Canada (currently at ETH, Zurich), and was initially tested in cell cultures and animal models in Dr. Nathalie Rivard’s lab at the Univ of Sherbrooke and at my lab (Verdu EF) at McMaster University. The idea of sequestering a molecule in the gut with an inert polymer is not new in medicine, and this approach has long been used for instance to lower cholesterol blood levels. What is ingenious from this polymer in particular, is that in addition to being poorly absorbed like other polymers, it targets with a high degree of specificity the gliadin molecule. This is what makes the approach unique for celiac disease.
When can we expect to see this compound being studied in people?
We are hoping that Phase 1 studies (these are safety studies performed in healthy subjects) could be ready to begin in 1-2 years.
What are the implications of this study for people with celiac disease?
Celiac disease is highly underestimated, particularly in North America, including Canada. The diagnosis of celiac disease in North America has an average delay of 10 years. Once diagnosed, celiac patients are told to follow a strict gluten free diet for life and are often considered “to be cured” with no appropriate follow-up. The ubiquitous use of gluten as a food additive, in cosmetic industry and in medications makes remaining “gluten free” an almost impossible task. There is considerable misunderstanding of the psychosocial and financial impact of this disease (undiagnosed and diagnosed) on patients, their families and the health care system. The availability of an inexpensive and safe adjuvant therapy would represent a boon to these patients and their families. As with most other luminal therapies being developed for celiac disease, such as enzymatic therapy, permeability modulation and polymer based strategies, BL-7010 is designed to be taken punctually, on demand, when the content of gluten in food cannot be ascertained.
How will this study contribute to future research for gluten-related disorders?
We hope this and other studies on the development of adjuvant therapies in celiac disease will help bring awareness of the disease, particularly in North America. Celiac disease is not only a highly relevant gastrointestinal disorder, but it is also a model where many disease pathways have been elucidated. Research in celiac disease can thus help shed light into the pathogenesis of other chronic inflammatory or autoimmune disorders such as inflammatory bowel disease and type 1 diabetes. I believe involvement of the pharmaceutical industry in celiac disease may establish a key connection between basic scientists and clinicians, which in turn, will increase awareness and contribute to build needed funding strategies to further stimulate interest and research in this complex disorder.
Visit the American Gastroenterology Association online to view the full study.