Probing the bowels of disease

Crohn’s and Colitis Foundation of Canada, Vertex Pharmaceuticals lead industry-academic quest to uncover biology of IBD

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TORONTO—For decades, patients who suffer from inflammatorybowel diseases (IBD) have mostly had therapies that address only specificsymptoms of their condition, but a new industry-academia collaboration inCanada is on a mission to change that with research aimed at identifying theunderlying disease mechanisms of IBD.
As patients and the medical community marked World IBD Dayon May 19, the Crohn's and Colitis Foundation of Canada (CCFC) and VertexPharmaceuticals Inc. announced that they will jointly provide funding for threeCanadian academic centers to further research into the biology of IBD,specifically its major types, Crohn's disease and ulcerative colitis. Thecollaboration is a unique in that it brings together a national healthcarecharity and a biotechnology company in Canada, which has a high incidence andprevalence rate of IBD.
"The burden of IBD is enormous in Canada. Over 200,000Canadians are affected by IBD, and the burden to our healthcare system isgreat," says Aida Fernandez, chief science and education officer at the CCFC.
In fact, in 2008, the CCFC released its report, "The Burdenof Inflammatory Bowel Disease in Canada," which found that IBD was almost asprevalent in Canada as epilepsy or diabetes. In 2008, costs covered by Canada'shealthcare system—expenses like hospitalization, surgery, medications andphysician visits—were estimated at $753 million. Other significant expenses arenot covered by the healthcare system—items like emergency visits, lab work andconsultations with nurse practitioners, dieticians and social workers—and it'sestimated that IBD incurs more than $1 billion every year in indirect costslike short- and long-term work absences, productivity losses and caregiver workabsences.
For Canadians and patients worldwide who suffer from IBD,treatments are usually limited to the use of anti-inflammatory steroids tocontrol disease flares as well as surgery such as bowel resection,strictureplasty or a temporary or permanent colostomy or ileostomy.
"Whatever we can do in terms of improving treatment optionsand quality of life for patients is very important. That's why we're fundingthis important, vital research," says Fernandez.
Founded in 1974 by a group of parents whose children werediagnosed with IBD who were concerned about the lack of funding for IBDresearch, the CCFC is now considered a world leader in IBD research funding,but the organization also focuses on raising awareness of IBD as a chronicdisease and addressing issues related to patient access to expensive IBD medications.Of particular concern to CCFC is advancing the understanding of the biology ofIBD in the hope that life-altering treatments can be found.
"Ultimately, we want to have something come out of theseresearch projects that will improve our understanding of the mechanisms behindIBD, something that is translatable and can lead to a drug target, that takesus to the next level of something that can be commercialized," says Fernandez."Sowing early seeds in this endeavor are important, and this is a stronginvestment in getting the right expertise."
To make this happen, the CCFC has chosen to partner withVertex, which is headquartered in Cambridge, Mass., but also has facilities inLaval, Quebec, as well as in the U.K. and San Diego. The company has more than45 scientists focused on IBD research. Vertex also has preclinical and clinicalprograms for cancer, multiple sclerosis, hepatitis C, cystic fibrosis,epilepsy, Huntington's disease, tuberculosis and influenza.
"Our interest in IBD is to do something that istransformative—to work at the core of the disease, and not just treat thesymptoms," says Dr. Louise Proulx, vice president and site head of VertexCanada. "We really believe this is going to take a network approach. We can'tdo everything in-house, and that's why we have chosen to work and collaboratewith academic institutions."
The academic research centers in this collaboration wereselected after a rigorous peer-review process. CCFC and Vertex then chose threelaboratories that are focused on probing the underlying biology of IBD: Dr.François Boudreau of the Université de Sherbrooke; Dr. Brian Coombes ofMcMaster University; and Dr. Scott Gray-Owen of the University of Toronto.
"There are over 100 genes linked to IBD," notes Fernandez."The fact that we know this is leading to a more comprehensive understanding ofthis complex disease. There is now a real momentum in personalized medicine andan investment of research in this area. Knowing which genes people carry willhelp us to customize treatments for them."
The projects will investigate the role of bacteria in IBDand the body's response to an imbalance of these bacteria in order to identifypotential targets for future IBD therapies.
"One of the things we hope to learn more about is how thisbacteria enters the body. Can we prevent entry by using a small-molecule, forexample? In two years, we hope to have a better understanding of the disease,which will give us new approaches to finding compounds," says Proulx.
The labs will each receive $200,000 in two rounds of grantfunding over the course of the two-year collaboration.
"We hope to do another round of applications this summer,and then fund up to another three new institutions," adds Proulx.
"Being able to work closely with other world-classscientists at Vertex and CCFC represents a promising new model for medicalresearch," said Scott Gray-Owen, who is a professor of molecular genetics atthe University of Toronto. "We're excited to have been chosen for this grantbecause it provides an opportunity to advance our understanding of a diseasethat affects so many Canadians."

The burden of IBD in Canada
Afflicting nearly 201,000 persons in Canada in 2008,inflammatory bowel disease (IBD) is more common than multiple sclerosis or HIV,about as common as epilepsy or type 1 diabetes and somewhat less common thanrheumatoid arthritis or schizophrenia.
The total cost of IBD in Canada in 2008 was at least $1.8billion. This is composed of direct medical costs ($753 million, or 41 percentof total costs) plus indirect societal costs ($1.06 million, or 59 percent oftotal costs). The average per-person cost is just over $9,000 per year.
Total costs are higher for Crohn's disease (CD) due togreater patient numbers. Per-person costs are also higher for CD, due to morefrequent hospitalizations and more costly medications: $9,950 per person peryear for CD and $7,900 for ulcerative colitis.
From "The Burden of Inflammatory Bowel Disease (IBD) inCanada," Crohn's and Colitis Foundation of Canada, 2008

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