Department of Medicine

Department of Immunology

Sinai Health

Lunenfeld-Tanenbaum Research Institute

Mount Sinai Hospital

Subheadline

Research from Sinai Health and U of T found early exposure to dogs is linked to a healthier gut and reduced risk of developing Crohn's disease

Dog lovers can attest to the range of benefits that come with having a canine companion, but improved gut health likely isn’t one of them.

That may be about to change following research from Sinai Health and the ��߲ݴ�ý that shows exposure to dogs during childhood is linked to beneficial changes in gut bacteria, gut permeability and blood biomarkers.

The study, published in Clinical Gastroenterology and Hepatology, found living with a dog between ages five and 15 is associated with a healthier gut microbiome and reduced risk of developing Crohn’s disease.

The research shines new light on how environmental factors influence the onset of Crohn’s – an inflammatory bowel condition – and could inform future prevention strategies.

For the study, researchers led by Kenneth Croitoru and Williams Turpin of Mount Sinai Hospital’s Centre for Inflammatory Bowel Disease (IBD) investigated how dozens of environmental factors impact the likelihood of developing Crohn’s as part of their overarching effort to be able to predict those at risk and potentially intervene early.

“The idea behind predicting someone's risk of disease is that you can then also begin to understand who you might want to do something to try and prevent disease,” says Croitoru, a clinician-scientist at the Lunenfeld-Tanenbaum Research Institute (LTRI), part of Sinai Health, and a professor of medicine and immunology at U of T’s Temerty Faculty of Medicine.

Croitoru notes the study doesn’t reveal why living with a dog makes someone less prone to Crohn’s disease. “We have established associations between environmental factors and Crohn’s and are now trying to understand how these environmental factors affect the triggering of the disease,” says Croitoru, who is also a gastroenterologist at Mount Sinai Hospital.

The study also found living with a large-sized family in the first year of life to reduce the likelihood of getting Crohn’s. It also found people who lived with a bird at the time of study were more likely to develop the disease.

Caused by inflammation in the gastrointestinal tract, Crohn’s disease can have far-reaching consequences on overall health and well-being. Its incidence among children under 10 has doubled since 1995, while the annual cost of inflammatory bowel disease to Canada is estimated at $5.4 billion per year, according to Crohn’s and Colitis Canada, a national non-profit.

The likelihood of getting Crohn’s is strongly influenced by genetics, but the environment also plays a role, says Croitoru, who holds the Canada Research Chair in Inflammatory Bowel Diseases. While we can’t change our genes, we can modify our surroundings and diet, for example, to potentially prevent the disease from occurring.

These findings come from the Genetic, Environmental and Microbial (GEM) Project, the largest study of its kind that seeks to identify potential triggers of Crohn’s disease.

Coordinated at Mount Sinai Hospital since 2008, the GEM Project has been collecting comprehensive medical and lifestyle data from over 5,000 healthy first-degree relatives of people who have Crohn’s and come from all over the world, including Australia, Canada, Israel, New Zealand, the U.K. and the U.S.

The project is funded by Crohn’s and Colitis Canada, the Canadian Institutes of Health Research and the Helmsley Charitable Foundation.

In the 15 years since the study began, over 120 people have developed the disease. “By understanding what is different about those who develop the disease, we should be able to predict who is at risk,” says Croitoru.

Previously, the group identified differences in the microbiome and other biomarkers in people who go on to develop Crohn’s and those who don’t.

In another recent report published in Gastroenterology, Sun-Ho Lee, a clinician-scientist at Mount Sinai Hospital’s IBD Centre and an assistant professor at the Institute of Medical Science at Temerty Medicine, used available data and machine learning to develop an “integrative risk score” that predicts the risk of Crohn’s with a high degree of accuracy.

But risk prediction is only the first step, says Croitoru, whose ultimate goal is to be able to intervene and prevent the disease from starting.

He and his team are now conducting research that seeks to devise and test strategies for prevention by, for example, adding supplements to the diet to promote a healthy microbiome.

“Sinai Health is committed to groundbreaking research and bringing those discoveries to patients," said Anne-Claude Gingras, director of LTRI and vice-president of research at Sinai Health.

“By integrating genetic, environmental, and microbial data, Dr. Croitoru and colleagues are paving the way towards personalized intervention strategies that could significantly reduce the incidence of Crohn’s disease.”

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle — Tue, 20 Aug 2024 16:17:45 +0000

Researchers propose biologically based classification system for Parkinson’s disease

rahul.kalvapalle Tue, 08/20/2024 - 12:17

Cutline

The "SynNeurGe" classification system for Parkinson's disease, proposed by researchers led by Professor Anthony Lang of the University Health Network and U of T, is based on three key biomarkers (photo by FG Trade/Getty Images)

Eileen Hoftyzer

Topic

Tanz Centre for Research in Neurodegenerative Diseases

Parkinson's

University Health Network

Subheadline

The classification system could enable advancements in the development of tailored treatments for Parkinson's disease

A team of researchers led by Anthony Lang of the University Health Network and the ��߲ݴ�ý have proposed a novel classification system for Parkinson’s disease that considers biological features and not just clinical symptoms.

The "SynNeurGe" system, described by Lang and collaborators in a paper published in The Lancet Neurology, classifies Parkinson’s disease based on three biomarkers: presence or absence of misfolded alpha synuclein protein, which is believed to cause or contribute to the underlying neurodegeneration; evidence of neurodegeneration using imaging techniques; and presence of gene variants that increase disease risk.

The researchers argue that such a classification system is necessary to advance the development of tailored treatments for Parkinson’s disease.

Professor Anthony Lang (supplied image)

“This is a complex group of disorders that may cause similar symptoms, but biologically they're very different,” says Lang, a senior scientist and Lily Safra Chair in Movement Disorders at UHN and a professor in the department of medicine and the Tanz Centre for Research in Neurodegenerative Disease at U of T’s Temerty Faculty of Medicine, where he holds the Jack Clark Chair for Parkinson’s Disease Research

“If we cannot find ways to subdivide patients biologically, then applying a therapy designed to affect one biological pathway may not be effective in another group of patients that doesn't have that same pathway involved – and we won’t really have precision or personalized medicine for Parkinson’s disease.”

Currently, Parkinson’s disease is classified based on clinical presentation and symptoms, but the disease can affect the brain for years, possibly even decades, before symptoms appear. For future therapies to treat the underlying disease rather than just the symptoms, patients will need early intervention and treatments tailored to the biological features of the disease, researchers say.

Similar approaches are being used for other diseases – cancer treatments vary not only by the location of tumors but also their molecular features, and the development of drugs for Alzheimer’s disease is increasingly guided by the specific biological mechanisms involved in the disease.

The SynNeurGe classification system, while based on the three key biomarkers, also considers whether clinical features are present. The different combinations of biomarkers classify the disease into various sub-types.

Lang and co-authors note that such a classification should only be used for research at present, although it will almost certainly have clinical applications.

“Eventually we will see a biological approach influencing clinical care, particularly when we finally have effective disease-modifying therapies,” says Lang. “We currently don’t know how important these biomarkers actually are.

"We need large-scale prospective studies of biomarkers, imaging and clinical features to interpret the results, give patients accurate information about their diagnosis and provide appropriate treatment.”

Lang’s team plans to start conducting such studies of cerebrospinal fluid, skin and blood to look for biomarkers of different sub-types of Parkinson’s disease that will help inform the classification system and the development of tailored therapies.

“Now is the time to think about these diseases not solely based on their clinical manifestations, but to look at the biology and try to separate different biological subtypes so we can ultimately improve treatment for this disease,” Lang says.

Professor Graham Collingridge, director of the Tanz Centre, says Lang and his team’s “landmark paper” is poised to have a significant impact on clinical practice around Parkinson's. “I am delighted that our researchers have played such a key role in this important biological classification,” Collingridge says.

Lang says research by Tanz Centre scholars has contributed significantly to the body of knowledge used to develop the proposed biological classification.

For example, Professor Ekaterina Rogaeva’s research on the genetics and epigenetics of Parkinson’s disease has shown that multiple genes and environments can influence Parkinson’s risk, highlighting the need to tailor therapies based on a patient’s genetic makeup.

Other researchers – including Anurag Tandon, Joel Watts, Martin Ingelsson and Gabor Kovacs – have been studying the role of misfolded alpha synuclein in neurodegeneration as well as cases of Parkinson’s disease where alpha synuclein is absent – which informed how Lang’s team included the protein in the classification.

New cancer treatment slows aggressive neuroendocrine tumours: Study

rahul.kalvapalle — Tue, 02 Jul 2024 13:45:10 +0000

New cancer treatment slows aggressive neuroendocrine tumours: Study

rahul.kalvapalle Tue, 07/02/2024 - 09:45

Cutline

Simron Singh, a medical oncologist at Sunnybrook Health Sciences Centre and associate professor in the Temerty Faculty of Medicine, led a study that found that radioligand therapy reduces the risk of advanced neuroendocrine tumour progression and death (photo by Kevin Van Paassen, Sunnybrook)

Topic

Sunnybrook Health Sciences Centre

Cancer

Subheadline

Research led by scientists at Sunnybrook Health Sciences Centre and U of T showed radioligand therapy to be an effective first-line treatment for advanced uncurable cancers

A novel approach for early cancer treatment known as radioligand therapy (RLT) has been shown to significantly reduce the risk of advanced neuroendocrine tumour progression and death, according to research led by scientists at Sunnybrook Health Sciences Centre and the ��߲ݴ�ý.

Results of the multi-centre clinical trial, which were published in The Lancet, provided evidence for the first time that RLT – when applied in the early stages after a patient’s diagnosis – slowed down the progression of aggressive grade 2 and 3 neuroendocrine tumours of the gastrointestinal tract.

The treatment was shown to extend the average time of “progression-free survival” from approximately 8.5 months to 22.8 months.

“This is the first study to show the effectiveness of RLT as the ‘first-line’ treatment with advanced uncurable cancer, or any cancer,” said the study’s global principal investigator Simron Singh, a medical oncologist at Sunnybrook and associate professor in the department of medicine at U of T’s Temerty Faculty of Medicine. “This trial is groundbreaking not only for patients with neuroendocrine cancers, but for all cancer patients as it has implications for the practice of cancer treatment broadly.”

Singh described RLT as a “game changer” in the treatment of cancer, which has traditionally been carried out by surgery, drugs or radiation. “While it’s technically radiation, it is given via a chemotherapy route through the blood until it reaches the precise location of the tumour,” said Singh, who is also an affiliate scientist at Sunnybrook Research Institute and co-founder of the Susan Leslie Clinic for Neuroendocrine Tumours at Sunnybrook’s Odette Cancer Centre.

RLT involves injecting radioactive isotopes – in this case, the drug Lutathera – through an IV. This method targets specific cancer cell receptors, delivering precise radiation to kill cancer cells while preserving healthy tissue.

The study evaluated the use of RLT earlier as a first-line (or “up front”) treatment for patients newly diagnosed with grade 2 or 3 advanced gastrointestinal neuroendocrine tumours. Although neuroendocrine cancer is uncommon, incidence is rising rapidly, and few treatments exist for patients. This cancer is resistant to most therapies, making it challenging to treat.

The results confirm the clinical benefit of earlier use of RLT for patients diagnosed with aggressive and life-threatening tumours, said Singh. “This is the next step in personalized targeted cancer therapy for patients, focused on more effectively killing cancer cells, while limiting the damage to surrounding healthy tissues.”

Further investigations of RLT as a therapeutic option are ongoing to evaluate overall survival and long-term safety, which will better define next steps for how this therapy will change cancer treatment world-wide.

The multi-site trial included investigators and participants from Canada, the United States, France, Germany, Italy, Netherlands, South Korea, Spain and the UK. An overview of the results was presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in January 2024.

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Nadia Radovini

Study by U of T, international researchers predicts worsening dengue spread in Mexico and Brazil

Christopher.Sorensen — Mon, 10 Jun 2024 15:11:55 +0000

Study by U of T, international researchers predicts worsening dengue spread in Mexico and Brazil

Christopher.Sorensen Mon, 06/10/2024 - 11:11

Cutline

Patients await treatment at an emergency medical care unit for dengue in Brasilia, Brazil (photo by Mateus Bonomi/Anadolu via Getty Images)

Gabrielle Giroday

Topic