New targets for treatment of diarrhoeal diseases discovered by RCSI researchers

Worldwide, almost 2 million children die each year as a result of infectious diarrhoea1, however, diarrhoeal diseases are also very common in developed countries. “Diarrhoea associated intestinal disorders, such as irritable bowel syndrome (IBS), Crohn’s disease, colitis, coeliac disease and microbial infections are a major health issue in Ireland.

It is estimated that between 40,000 and 50,000 people visit their local Gastroenterology clinic each year2 seeking treatment for diarrhoea. The cost to the Irish economy in terms of healthcare costs and lost working days is immense,” commented Dr Stephen Keely, senior author on the study and Associate Director of the RCSI Molecular Medicine Lab at Beaumont Hospital.

Explaining the findings of the research study, Dr Keely said: ‘Current treatments for intestinal diseases are not targeted specifically enough and as a result can be ineffective or have serious side effects. Working with researchers in UCD and TCD, we have discovered that a type of protein, known as hydroxylases, play a key role in regulating water and salt transport in the intestines. Our experimental results suggest that by inhibiting the activity of these proteins, diarrhoea can be prevented. The discovery gives us a promising new target for the development of drugs to treat intestinal diseases that have diarrhoea as a primary symptom. Because such drugs would act directly on the cells responsible for controlling water movement in the intestine, they would potentially have better outcomes and reduced side effects for patients,” Dr Keely concluded.

The lead author on the paper is Joseph Ward who conducted the research as part of his PhD studies along with Dr Karen Lawler and Dr Keely from the Molecular Medicine Laboratories in RCSI. The team also collaborated with Prof Padraic Fallon from the Institute of Molecular Medicine, Trinity College Dublin, and Prof Cormac Taylor of the Conway Institute at University College Dublin.

This work was published in the Federation of American Societies for Experimental Biology (FASEB) Journal in October 2010 and was funded by Science Foundation Ireland and the Higher Education Authority’s Programme for Research in Third Level Institutions (PRTLI) Cycle 4, as part of the National Biophotonics Imaging Platform (NBIP) Ireland.

Full bibliographic information
Ward J.B.J., Lawler K., Amu S., Taylor C.T., Fallon P.G., Keely S.J (2010). Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea. FASEB Journal, October 2010

fj.10-166983 http://www.fasebj.org/content/early/2010/10/27/fj.10-166983.abstract