St. Vincent’s Hospital Immunology Centre Mouse Model
From February 2000 to August 2008, The Gutsy Group provided $131, 250 to fund the St. Vincent’s Hospital Immunology Centre Mouse Model. This project centred on a mouse model that mimicked human ulcerative colitis.
The research was carried out under the direction of Professor Tony d’Apice, Professor of Immunology at St. Vincent’s Hospital. The Professor’s main research was humanising mice and pigs so animal kidneys may be successfully transplanted into humans in the future. Mice were inserted with the human gene 1-2 fucosyltransferase in the course of different research. Unexpectedly, and through serendipity, these mice developed colitis. As a result, this event enabled extensive research into the mechanism of the colitis to be performed on this animal model over the next nine years.
This research was conducted by four research fellows, Dr Ashley Miller, Dr Steven Brown, Dr Greg Moore and Dr Mark Lust, all of whom were awarded PhDs for their research. Three of the researchers received gold medals for this research into gastroenterology. Through this research it was demonstrated that these mice had abnormal thymus glands with consequent major effects on the immune system, a world first.
The Mouse Model of Ulcerative Colitis
In the transgenic Mouse Model of Ulcerative Colitis (hFUT1), the human gene for Alpha 1-2 fucosyltransferase, inserted into the normal DNA of the mouse, produced spontaneous colitis that was similar to the human disease, ulcerative colitis. The mice developed severe diarrhoea, wasting and early death.
As a result of extensive research with the model, it was found that this genetic manipulation changed the type and shape of the sugar molecules that protruded from the surface of many cells, including lymphocytes, which are the major cells that control immunity. It was found that this abnormality caused:
- Chronic inflammation of the colon
- Defect in the mucus produced by the colon (mucus is thought to be a factor in preventing bacteria from invading the wall of the colonoscopy)
- Aberrant development of lymphocytes. Immature lymphocytes are processed by the thymus gland, which lies in front of the heart. Normal lymphocytes pass through the thymus, and have a number of sugar molecules attached to their surface, and then circulate back into the tissues of the body so they can carry out their normal immune function. In this mouse model the thymus gland was small and under-developed, (atrophic), and consequently the lymphocytes had abnormal surface markers, and therefore loss of their normal immune function.
This is the first time that an animal model of colitis had been developed due to a thymic abnormality.
It was found that the colitis in this model could be reversed by irradiating the mice and transplanting normal immune system using bone marrow from a normal mouse. Furthermore, if the abnormal mice were bred in a germ-free environment (have no bacteria in the gut), they did not develop colitis.
Finally, many experiments were performed to detect coagulation abnormalities, but no significant defects were identified.
Further information can be found in the articles published in the Inflammatory Disease Journal:
Brown, S.J., Miller A.M., Cowan P.J., Slavin J, Connell W.R.,. Moore G.T., Bell S., Elliott P.R., Desmond P.V., d’Apice A.J., Altered Immune System Glycosylation Causes Colitis in Alpha1,2-fucosyltransferase Transgenic Mice, Inflammatory Bowel Disease 2004 Sep; 10(5):546-56.
Moore, G.T., Brown, S.J., Winterhalter A.C., Lust M., Salvaris E.J., Selan C., Nandurkar H.H, Desmond P.V., Cowan P.J., d’Apice A.J., Glycosylation Changes in hFUT1 Transgenic Mice Increase TCR Signaling and Apoptosis Resulting in Thymocyte Maturation Arrest, Mol. Immunology 2008 Apr; 45(8):52401-2410.
Health Economics Group Cost of Inflammatory Bowel Disease in Australia
In 2005 and 2006 The Gutsy Group provided funding of $20,000 to the Health Economics Group at The University of Melbourne. The analysis was carried out by Stephen Colgan, research fellow with the Health Economics Group Programme Evaluation Unit, under the tutelage of Associate Professor Rob Carter. This research was undertaken to assess the financial burden of inflammatory bowel disease in Australia, to highlight the future impact of IBD, and to assist in the raising of funds.
The final report on the cost of inflammatory bowel disease was tabled in March, 2006. The report was the first comprehensive assessment of the costs of IBD in Australia and the most complete economic assessment of the burden of the disease. Some of the key findings were:
- The prevalence of IBD in Australia was 360 per 100,000, which second highest only to Canada.
- The total cost of IBD in Australia in 2005 was approximately$267 million, $220 million related to medical costs, and $40 million to lost wages.
Please contact us if you would like to obtain a copy of the report.
Geelong Incidence Study
In 2007 and 2008, in conjunction with the Bennelong Foundation, The Gutsy Group contributed $70,000 to a study undertaken by research fellow, Dr Jarrad Wilson from the Department of Gastroenterology at St. Vincent’s Hospital, Melbourne. The funding was used to produce the first prospective population-based Australian incidence and study of inflammatory bowel disease.
As a result of this research, Dr Jarrad Wilson was awarded the gold medal in 2008 by the Gastroenterological Society of Australia for the best clinical research for a junior investigator.
The research was carried out in Greater Geelong, Victoria. The risk population was 259,000, and all 274 general practitioners and specialists working in this area were contacted every two months to identify all new cases occurring in one year. The results were:
- 75 new cases of inflammatory bowel disease – 46 Crohn’s disease and 29 ulcerative colitis. The peak incidence occurred between 20-24 years-of-age, with 42 females and 33 males.
- The inflammatory bowel disease incidence rate of 29.3 per 100,000 is the second highest ever reported in the literature, and the Crohn’s disease incidence rate of 17.8 per 100,000 is the highest ever reported.
The Post-Operative Crohn’s Endoscopic Recurrence (POCER) Study
In 2010, through the generous support of the Tattersalls George Adams Foundation,The Gutsy Group, Inc. committed $80,000 to a clinical study into the prevention of Crohn’s disease after surgery. The research project was titled The Post-Operative Crohn’s Endoscopic Recurrence (POCER) Study. This project was led by Professor Michael Kamm and Dr Peter de Cruz from St. Vincent’s Hospital, Melbourne
This project was chosen as it represented a novel approach to a common problem and was the first study of its type. It had the potential to enhance both the clinical and basic science knowledge base regarding the prevention of Crohn’s after surgery. This project was jointly funded with the NMHRC which separately donated $392,000 to the project.
The project’s results had the potential to affect clinical practice in the near future. The basic science component of exploring the microbiological reasons why Crohn’s disease may reoccur after an operation has never been studied. The results would also potentially illuminate the underlying mechanisms in the intestinal immune system responsible for causing Crohn’s disease. The study involved over 20 teaching hospitals in Australia and New Zealand over three years.
The use of faecal microbiota transplantation (FMT), as a therapy for acute ulcerative colitis
The IBD research projects funded for Professor Jane Andrews and her team at The Royal Adelaide Hospital focuses on a topic that has gained much publicity recently. FMT is an evidence-based strategy for treating a particular form of infectious colitis known as Clostridium Difficile. Whether it is effective for the treatment of IBD is still unknown.
Professor Andrews’ team is conducting a randomised-controlled trial of FMT in patients who are acutely unwell with ulcerative colitis. To date, 50 patients have been recruited in the study, and results will hopefully be available next year.
As well as looking at the effect of FMT in recipients (patients) the study is looking closely at the characteristics of the donor stool that make it more likely for a patient to respond. Emerging data suggests that not all donor stool is equal!
Gutsy Group funding was also helpful in the study team successfully obtaining National Health and Medical Research Council (NHMRC) funding to conduct associated research into the microbiota (gut bacteria) in ulcerative colitis patients. There has been great recent interest in FMT amongst patients and the media, but well-designed studies such as this one, are required to confirm its validity, or otherwise, as an effective treatment for IBD.
A novel thiopurine to effect fast, more tolerated and safe immunosuppression
The successful applicant for 2012/13 was from the University of Queensland and the research group of Professor Timothy Florin. This study is investigating the role of a newer immunomodulator, thioguanine, in managing Inflammatory Bowel Disease (IBD), and incorporates both basic science and clinical aspects. The scientific committee felt this study could bring exciting results at a national and international level and has the most potential for improving the quality of life of patients living with IBD. The Gutsy Group, Inc. has committed $150,000 over three years and looks forward to updating our supporters as results come to hand.