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LONDON, ON - In a study involving 542 Crohn’s disease patients, researchers at Lawson Health Research Institute examined whether a patient’s DNA can be used to identify their risk of severe disease. They found that patients with a genetic variant in a gene called FXR (farnesoid X-receptor) are much more likely to need surgery and to need it earlier in their care journey. Surprisingly, they found that women with the genetic variant are at an even higher risk than men.

Crohn’s disease is an often debilitating condition that affects one in every 150 Canadians. The condition is characterized by intestinal inflammation caused by unnecessary attacks from the body’s immune system. It’s a disease that can behave and progress differently from one person to the next, with some requiring surgery to remove affected parts of the intestine.

“While medications are prescribed to manage Crohn’s disease, physicians have to balance the risk of side effects with the risk of undertreating severe cases of the disease,” explains Dr. Aze Wilson, Associate Scientist at Lawson Health Research Institute and Gastroenterologist at London Health Sciences Centre (LHSC). “In order to personalize treatment, it would be great to have a tool for identifying which patients will have the most severe cases of illness.”

Dr. Wilson and her colleagues became interested in the FXR gene because of its role in intestinal health. The FXR gene is a part of human DNA that controls how we process drugs and has also been linked to how well our intestines work. The research team suspected that variation in the gene could lead to poorer outcomes in Crohn’s disease patients. 

“Given the importance of FXR to intestinal health, we wanted to see whether it plays a role in disease severity and we discovered that it does,” says Dr. Wilson. “Our findings suggest that genetic testing could be used to identify patients at a high risk of poor outcomes. This would allow physicians to tailor treatments to give patients the best chance at success.”

The team also discovered that women who carried the genetic variant were at the highest risk of needing surgery and the highest risk of early surgery, even when compared to men with the genetic variant. Struck by this finding, they conducted further testing using laboratory-based cell models. They found that estrogen (a female sex hormone) in combination with the genetic variant reduced the function of FXR even further. 

“Differences between men and women with Crohn’s disease are not often considered in research or clinical practice. We apply treatments in the same way to both sexes, which may not be the best approach,” explains Dr. Wilson. “We identified a group of women who may benefit from a different approach to care. The study highlights the need for evaluating the effect of biological sex on disease and the interaction it may have with our DNA.”

Looking forward, the team hopes to further explore the effect of this genetic variant on intestinal health using laboratory-based cell models. They also hope to assess the value of genetic testing as a tool for informing treatment decisions made by patients and their physicians. 

“One of our larger goals as a research group is to develop a personalized care plan for patients with Crohn’s disease and ulcerative colitis – one that integrates genetic information and other biomarkers to improve how care is delivered to these patient populations,” notes Dr. Wilson. 

The study, “Genetic variation in the farnesoid X-receptor predicts Crohn’s disease severity in female patients,” is published in Nature’s Scientific Reports.  

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Dr. Aze Wilson, Associate Scientist at Lawson Health Research Institute and Gastroenterologist at London Health Sciences Centre (LHSC)

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LONDON, ON – At a virtual event today, a research team led by Lawson Health Research Institute announced details of a new project aimed at better understanding how many people in Canada are homeless and who they are. Developing more accurate sources of data related to homelessness helps ensure the proper supports and services are available.   

“The homeless experience varies significantly across Canada, especially within different rural and remote regions of the country,” says Dr. Cheryl Forchuk, Assistant Scientific Director at Lawson and Distinguished University Professor at Western University. 

With funding from the Public Health Agency of Canada, the Homelessness Counts research project builds on past work looking at how existing databases, such as provincial health data, could be better integrated and used as a more accurate, accessible and cost-effective way to determine homelessness.  

Many communities rely on shelter data, but not all regions have shelters and not all people who are experiencing homelessness use shelters even when available. There is also a standard “point in time” method that requires potentially hundreds of volunteers to go out and actually count the people in that area who are homeless. “Generally, these methods will still miss people who are temporarily staying with others or living in rough or abandoned areas, and is limited to a single point in time – often just one day of counting. It’s often not feasible for smaller communities to do this due to the effort required and it’s a population often missed in our census data,” explains Dr. Richard Booth, Scientist at Lawson and Associate Professor at Western. 

In the initial stages of the project, the team is holding focus groups with several representative communities across Canada to learn more about how data is tracked and accessed. They will consult with groups providing services such as homeless serving agencies, mental health and addiction agencies, hospitals, emergency services and municipal governments. Individual interviews will also be held with people with lived experience of homelessness. 

“To offer effective and efficient services, we need to know how many people are experiencing homelessness, along with their characteristics, location and needs. Right now, it’s difficult to track if things are getting better or worse, or simply changing, and if efforts to reduce the homeless population are making a difference. We don’t fully know the unique challenges of the ‘invisible homeless’ or if different subgroups are emerging,” says Dr. Booth.  

More demographics could be regularly included in the data, for example gender, ethnicity, sexual orientation, involvement in the criminal justice system, psychiatric diagnoses, physical diagnoses and housing status.  

The team will bring together this information with existing datasets to improve the performance of an algorithm previously developed through a provincial research study, as well as insights gleaned from a rapid report on COVID-19 and homelessness. Machine learning will be used to generate enhanced risk and burden modeling.  

Dr. Forchuk adds that “homelessness is a complex social problem that touches on many different systems. It is made even more difficult to tackle when we have big gaps in the data. Our hope is to prototype a centralized surveillance system that can be scaled up across Canada to help make the right services available in the right places.”  

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Leaking valves are a common condition amongst cardiac patients

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LONDON, ON- Researchers at Lawson Health Research Institute and Western University had a leading role in a new global study that will change the way surgeons repair leaky valves in the heart. It’s one of the most common heart valve conditions, where many patients don’t even realize they have a leaky valve and are asymptomatic, often presenting to doctors once they are late stage into the disease.

“If the leak in the mitral valve is not repaired, a patient will have problems with fluid retention, shortness of breath and heart failure,” Says Dr. Michael Chu, Lawson Scientist and Chair/Chief of the Division of Cardiac Surgery at Western’s Schulich School of Medicine & Dentistry. “That will then lead to complications requiring hospitalization and eventually an increased risk of death.” Dr. Chu is also a cardiac surgeon at London Health Sciences Centre (LHSC).

There are two related valves in the heart that can potentially leak and lead to further complications, the mitral valve and the tricuspid valve. Traditionally, the mitral valve is surgically repaired first, with the belief that it will lead to improvements in the tricuspid valve, however, scientists have discovered that isn’t always the case. “What we were concerned with was, if we repair the mitral valve only, will the tricuspid valve still leak?” 

To answer that question, the Division of Cardiac Surgery research team engaged in a multicenter, randomized trial run by the Cardiothoracic Surgical Trials Network, an important clinical trials network from the National Heart, Lung, and Blood Institute in the United States. The study took place in 39 hospital sites across the world with more than 400 cardiac patients. Dr. Chu and his team in London worked with patients through LHSC to be the top recruiting hospital and research team in this study.  Patients were randomized in the trial, half receiving mitral valve repair alone, and half receiving mitral and tricuspid repair surgery at the same time. 

“What we found two years after the operations was that the group that had both mitral and tricuspid repair had significantly less severe residual leak of the tricuspid valve,” explains Dr. Chu. “These findings suggest that concomitant tricuspid repair is extremely effective and those patients who present with a tricuspid leak, should have both valves repaired at the same time.”

The study findings have been published in the New England Journal of Medicine, which has a high impact worldwide within the medical community, especially when it comes to medical practices. Dr. Chu, joint first author in the paper, believes these findings will have an important impact worldwide to how surgical teams repair leaking heart valves, and is extremely proud that this top tier, practice-changing research is being performed at Western’s Schulich School of Medicine and LHSC.

Moving forward, the next steps will be to follow these patients for five years and further investigate various aspects of the study, with the ultimate goal of improving long term outcomes for patients.

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