Sunnybrook Health Sciences

Subheadline

Researchers say physicians should consider prescribing lower-risk antibiotics for patients when clinically appropriate

Two classes of commonly prescribed oral antibiotics are associated with the greatest risk for severe drug rashes that can lead to emergency department visits, hospitalizations and even death, according to a study by researchers at ICES, Sunnybrook Research Institute and the �ؿ�ζSM.

The study, published in the journal JAMA, found that sulfonamides (“sulfa drugs”) and cephalosporins were associated with the highest risk of reactions. The findings were based on a case-control study that used health-care data from ICES of adults 66 years or older who received a prescription for at least one oral antibiotic between 2002 and 2022 in Ontario.

Serious cutaneous adverse drug reactions (cADRs), or severe drug rash, are a group of rare but potentially life-threatening delayed reactions involving the skin and, often, internal organs. Some of these reactions carry mortality rates from 20 to 40 per cent. While many different classes of drugs can cause serious reactions, antibiotics are among the most commonly reported triggers.

The researchers say physicians should consider prescribing lower-risk antibiotics for patients when clinically appropriate.

“Clinicians have speculated that certain antibiotics carry greater risk for these severe reactions, but no study has ever confirmed these claims,” says Erika Lee, an allergist and a trainee with ICES and the Temerty Faculty of Medicine’s Eliot Phillipson Clinician-Scientist Training Program.

“Our objective was to explore the risk for cADRs in a population of older adults, who tend to receive disproportionately more antibiotic prescriptions than younger adults.”

Over the study period, 21,758 adults had an emergency department visit or hospitalization for a serious reaction following oral antibiotics and were matched with 87,025 controls who did not have a reaction.

“The good news is that most patients who visited the hospital with these reactions were discharged without being admitted, so that should be reassuring to providers and patients,” says Lee. “However, of those who were admitted to hospital with the most severe reactions, 20 per cent were treated in the ICU and five per cent of hospitalized patients died, which underscores the need for careful prescribing practices.”

The most commonly prescribed antibiotics were penicillins (29 per cent), followed by cephalosporins (18 per cent), fluoroquinolones (17 per cent), macrolides (15 per cent) nitrofurantoin (nine per cent) and sulfonamides (six per cent). Less commonly prescribed antibiotics were grouped together and accounted for seven per cent of prescriptions.

Other key findings include:

There were two antibiotic reaction-related hospital visits for every 1,000 antibiotic prescriptions dispensed
About one in eight patients who arrived at the emergency department with antibiotic-related reactions were hospitalized, likely because their reactions were more severe or because of concerns about potential complications
Twenty per cent of hospitalized patients with the most severe forms of reactions were treated in a critical care unit, and five per cent of those patients died

“While rare, these severe drug reactions can be life-threatening. Patients should be aware of rash, fever and other symptoms, which can start weeks after a prescription has been started and even after the course of antibiotics has stopped,” says David Juurlink, a staff internist and head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre, senior core scientist with ICES and professor in the department of medicine in the Temerty Faculty of Medicine.

“It’s also one more reason why antibiotics should be prescribed only when they’re truly needed.”

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ICES

Breast milk may have protective effects against COVID-19: Researchers

Christopher.Sorensen — Mon, 29 Jan 2024 18:38:03 +0000

Breast milk may have protective effects against COVID-19: Researchers

Christopher.Sorensen Mon, 01/29/2024 - 13:38

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Samantha Ismail led a study by researchers at U of T and its partner hospitals that looked for SARS-CoV-2 antibodies in human breast milk (supplied image)

Topic

COVID-19

Laboratory Medicine and Pathobiology

Vaccines

Subheadline

“COVID-19 vaccination and infection result in antibodies in human milk that have neutralizing capacity"

The COVID-19 pandemic was an especially harrowing time for pregnant people and new parents.

The uncertainties about how the new coronavirus could affect a pregnant person and their developing fetus – not to mention being cut off from support networks – left many expecting parents feeling isolated and anxious.

“It was a very surreal time,” says Jenny Doyle, a Toronto mom who gave birth to her first child, Elliott, in 2020 and spent hours researching how the first vaccines made available the following year might affect her and her child. “At the time, vaccines for infants were still so far away. I remember hoping that some of the protection I’d received from my vaccine would pass through to Elliott.”

Now, new findings from a study led by researchers at the �ؿ�ζSM and its partner hospitals suggest that is the case.

Published in the American Journal of Clinical Nutrition, the study looked for antibodies against SARS-CoV-2 in breast milk from three different cohorts: individuals who contracted COVID-19 while pregnant or nursing, routine milk bank donors and individuals who received two doses of the COVID-19 vaccine while pregnant or nursing.

The researchers detected antibodies in breast milk from roughly half of the people in the COVID-19 positive cohort. That’s compared to less than 5 per cent of routine milk bank donors, who did not have any known exposures to COVID-19. In the vaccinated cohort, they found that antibodies levels were higher in people who had received the Moderna vaccine compared to those who had received the Pfizer-BioNTech vaccine. Unexpectedly, people who had shorter intervals between their first and second doses had higher antibody levels than those who waited longer between their immunizations.

“That finding definitely surprised me,” says Samantha Ismail, the study’s first author who completed her master’s degree in the lab of Deborah O’Connor, the Earle W. McHenry Professor and chair of Temerty Medicine’s department of nutritional sciences. “In [blood] serum, it’s the other way around where longer intervals between doses typically result in higher antibody levels, suggesting that something different is happening in this lactating population.”

In addition to Ismail and O’Connor, the study was led by Sharon Unger, medical director of the Roger Hixon Ontario Human Milk Bank at Sinai Health and a U of T professor of medicine and nutritional sciences, and Susan Poutanen, microbiologist and infectious disease consultant and Sinai Health and U of T associate professor of laboratory medicine and pathobiology.

The team took the study one step further by showing that some breast milk samples could prevent SARS-CoV-2 from infecting cells in a lab setting. Within the COVID-19 positive cohort, milk that contained antibodies against the virus were more likely to be neutralizing and immunization with the Moderna vaccine was associated with a stronger neutralizing capacity than the Pfizer-BioNTech vaccine.

The researchers also found a small but significant number of breast milk samples that prevented SARS-CoV-2 infection despite having undetectable levels of antibodies, suggesting that there could be other components in human milk that are active against SARS-CoV-2.

While these findings provide strong evidence to support the potential protective effects of human milk, Ismail cautions that the study alone is not enough to prove that breast milk provides tangible protection against COVID-19.

“COVID-19 vaccination and infection result in antibodies in human milk that have neutralizing capacity, but we don’t know for sure how the neutralizing capacity seen in the lab translates to protection in infants,” says Ismail, who is now a second-year medical student at U of T.

She points out that previous studies have shown a clear protective effect of antibodies in human milk against other viruses like enterovirus and rotavirus. To date, such studies have not been done with COVID-19.

Even so, the findings provide reassuring news to parents like Doyle, who breastfed her son longer than she had intended to ensure that he was still getting breast milk when she received her second COVID-19 vaccine.

“Trying to figure out how to protect this tiny being in that scary and bleak time, I was grasping at every little piece of information and whatever little piece of hope we had.”

The study was supported by the Canadian Institutes for Health Research and was a collaboration between the department of microbiology at Sinai Health System/University Health Network, the Roger Hixon Ontario Human Milk Bank at Sinai Health System and the Toronto High Containment Facility, where the live SARS-CoV-2 neutralization studies were completed.

It involved contributions from several members of the Emerging and Pandemic Infections Consortium, a U of T institutional strategic initiative. In addition to O’Connor, Poutanen and Unger, they include Scott Gray-Owen, of Temerty Medicine’s department of molecular genetics, Samira Mubareka, of Sunnybrook Health Sciences Centre and Temerty Medicine’s department of laboratory medicine and pathobiology, and Jennie Johnstone and Allison McGeer – both of Sinai Health and Temerty Medicine’s department of laboratory medicine and pathobiology.

Patients operated on by female surgeons had lower health-care costs: Study

Christopher.Sorensen — Fri, 01 Dec 2023 16:18:45 +0000

Patients operated on by female surgeons had lower health-care costs: Study

Christopher.Sorensen Fri, 12/01/2023 - 11:18

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(photo by Chris Ryan/Getty Images)

Topic

A new study suggests that patients treated by female surgeons, across many different types of procedures, have lower total health-care costs than patients treated by male surgeons.

The population-based cohort study, published in JAMA Surgery, included over one million adult patients in Ontario who were undergoing 25 common elective and emergency surgeries between 2007 and 2019. The health and demographics data were linked and analyzed at ICES, an independent, non-profit research institute.

Prior studies have also found that patients treated by female physicians have better health outcomes than those treated by male physicians when it comes to mortality, surgical complications, re-operations and readmission to hospital after the surgery.

"It could be that managing potential complications following surgery will contribute to greater costs for male surgeons," says lead author Christopher Wallis, a urologic oncologist at Sinai Health and University Health Network who is an assistant professor in the �ؿ�ζSM’s department of surgery in the Temerty Faculty of Medicine.

Researchers Angela Jerath and Christopher Wallis (supplied image)

Costs for female surgeons were significantly lower at 30 days, 90 days and one year following surgery compared to those treated by male surgeons, according to the study. This corresponds to a relative cost difference of 10 percent.

"These differences represent potentially large savings for the health-care system," says Angela Jerath, a scientist at Sunnybrook Research Institute and adjunct scientist at ICES who is an associate professor in Temerty Medicine’s department of anesthesiology and pain medicine. "We need further qualitative research to better understand behavioural and sociocultural factors that may underpin these cost differences."

"There's also a need to improve recruitment and retention of female surgeons, as evidence shows dwindling numbers the higher up you go in surgical departments," adds Wallis.

"Creating more equitable and inclusive working environments would contribute to greater diversity and could have a positive impact on the health of patients undergoing surgery."

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. It was also supported by U of T’s Data Sciences Institute, an institutional strategic initiative.

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Misty Pratt

Research may explain why men are more likely to experience severe cases of COVID-19

Christopher.Sorensen — Tue, 03 Oct 2023 15:11:29 +0000

Research may explain why men are more likely to experience severe cases of COVID-19

Christopher.Sorensen Tue, 10/03/2023 - 11:11

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Haibo Zhang, a researcher at Unity Health Toronto and U of T, led pre-clinical research that suggests why males are more likely to experience worse outcomes from COVID-19, opening the door to potential new treatments (photo by Julia Soudat)

Topic

Graduate Students

St. Michael's Hospital

Subheadline

Pre-clinical study points to ACE2 protein as a key contributor to the differences in COVID-19 outcomes between males and females

A new study by a team of researchers at the �ؿ�ζSM’s Emerging and Pandemic Infections Consortium (EPIC) has uncovered biological reasons underlying sex differences in COVID-19 outcomes, offering a promising new strategy to prevent illness.

The pre-clinical research, published in the journal iScience, has yet to be replicated in humans, but points to the ACE2 protein as a key contributor to differences in COVID-19 outcomes between males and females.

During the early days of the pandemic, clinicians noticed that males were more likely than females to be hospitalized or admitted to the ICU or to die from COVID-19 despite having similar infection rates.

This pattern held true across all age groups and in countries around the world.

“COVID-19 severity and mortality are much higher in males than in females, but the reasons for this remain poorly understood,” says study senior author Haibo Zhang, a staff scientist in the Keenan Research Centre for Biomedical Science at St. Michael’s Hospital, Unity Health Toronto, and a professor of anesthesiology and pain medicine, and physiology in U of T’s Temerty Faculty of Medicine.

“That was the driving force for our work.”

The study was a collaborative effort through EPIC, a U of T institutional strategic initiative that involves five hospital research partners – the Hospital for Sick Children (SickKids) Research Institute, Lunenfeld-Tanenbaum Research Institute at Sinai Health, Sunnybrook Research Institute, Unity Health Toronto and the University Health Network (UHN) – to facilitate an integrated and innovative response to high-risk, high-burden infectious diseases.

From left: PhD student Jady Liang, co-lead author of the study and Professor Haibo Zhang (photos supplied)

Located on the cell’s outer surface, ACE2 plays an important role in controlling blood pressure and inflammation and protecting organs from damage caused by excess inflammation. During a SARS-CoV-2 infection, the coronavirus spike protein locks on to ACE2 to enter the cell.

The gene encoding the ACE2 protein is located on the X chromosome, which means that females have two copies of the gene and males only have one.

In times of health, the extra copy of the gene for ACE2 doesn’t appear to make a difference – Zhang and his team found similar levels of ACE2 protein in healthy males and females.

Following a SARS-CoV-2 infection, however, they observed a dramatic decrease in ACE2 in males while levels remained consistent in females, suggesting that the additional copy of the ACE2 gene on the X chromosome is helping to compensate and maintain high protein levels in females.

The changes in ACE2 levels were also correlated with a drop in estrogen hormone signalling in males, which could also contribute to the sex-specific differences in COVID-19 outcomes.

To test whether low levels of ACE2 were responsible for the more severe outcomes seen in males with COVID-19, the researchers devised a therapeutic approach using an inhaler to deliver lab-made ACE2 proteins directly into the lungs. Males who received a daily puff of ACE2 after SARS-CoV-2 infection had less virus in their lungs, less lung injury and higher levels of estrogen signalling.

Together, these results paint a clearer picture of how the extra copy of the ACE2 gene and higher estrogen levels in females work together to protect them from experiencing more severe COVID-19.

“A common misconception is that an increased presence of ACE2 receptors would result in a higher infection rate,” says Zhang.

“However, the enhanced activation of ACE2 in females actually serves as a compensatory mechanism during infection that’s aimed at safeguarding the lungs and other vital organs from potential damage.”

In males who lack the second copy of the gene, much of the existing ACE2 gets co-opted by SARS-CoV-2 during an infection. As a result, there is not enough of the protein to fulfil its usual functions of tamping down inflammation and preventing organ damage.

The extra dose of ACE2 delivered by inhaler serves as a decoy to glom onto the coronavirus, thereby preventing it from entering cells while also keeping the native ACE2 proteins free to exert protective effects.

Beyond the thrill of discovery, Zhang says he is excited by the potential implications of these findings, which are the first to demonstrate the effectiveness of inhaling ACE2, on preventing and treating COVID-19 in humans.

He imagines a scenario where people who are entering high-risk situations – boarding an airplane or attending a large in-person conference, for example – might take a puff of ACE2 to protect their lungs from the virus. Similarly, the treatment could also be given to people after infection to reduce the risk of hospitalization and death.

“By using the inhaler, ACE2 remains in the lungs at a sustained, low concentration over an extended period, where it can neutralize the virus even before it enters into our cells. We anticipate that our research will motivate individuals to contemplate this faster and more efficacious strategy for both prevention and treatment of COVID-19 in humans,” says Zhang.

Zhang worked with fellow researchers Samira Mubareka (Sunnybrook, Temerty Faculty of Medicine), Theo Moraes (SickKids, Temerty Faculty of Medicine) and Mingyao Liu (UHN, Temerty Faculty of Medicine). Much of their work took place in the Toronto High Containment Facility (THCF), which is the only containment level 3 research lab in the Greater Toronto Area and the largest in the province.

Having access to the THCF allowed Zhang and his team to pivot quickly during the early months of the pandemic and apply their expertise in lung physiology and disease to answering rapidly emerging questions about COVID-19.

Jady Liang, the co-lead author of the new study, had just started her PhD with Zhang when the pandemic started. She recalls the stress and intensity of training and working in the THCF during that time but credits EPIC staff and other THCF users with helping her become comfortable with the processes and protocols.

“It was a lot of hard work from everyone on the team during the pandemic, especially during the first wave,” says Liang, who is now a fourth-year PhD student in the department of physiology.

“We need a lot of people with expertise in different fields to work together so that we can advance and be prepared for the next pandemic.”

The study received support from the Canadian Institutes of Health Research, among others.

U of T home to new hub that will strengthen Canada’s pandemic preparedness and increase biomanufacturing capacity

Christopher.Sorensen — Thu, 02 Mar 2023 15:42:11 +0000

U of T home to new hub that will strengthen Canada’s pandemic preparedness and increase biomanufacturing capacity

Christopher.Sorensen Thu, 03/02/2023 - 10:42

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(photo by Jonathan Nackstrand/AFP/Getty Images)

Topic

Our Community

Bioinnovation

Leah Cowen

Health

A new national hub focused on enhancing Canada’s ability to respond quickly, effectively and equitably to future pandemics has become a reality with $2 million in funding from the Canada Biomedical Research Fund.

Led and anchored by the �ؿ�ζSM, the Canadian Hub for Health Intelligence and Innovation in Infectious Diseases (HI³) is a collaborative, multi-disciplinary and multi-sector coalition of more than 80 partners. It will provide a powerful network to support a robust domestic pipeline of life-saving vaccines and therapeutics targeting existing and emerging infectious threats.

Linking the innovation engine and resources of eight Ontario universities and six research hospitals with regional and national commercialization, biomanufacturing and pharmaceutical partners, the HI³ hub will enable the country to be more prepared, resilient and independent in facing future health challenges.

The hub is led by co-directors Jen Gommerman and Scott Gray-Owen, professors of immunology and molecular genetics, respectively, in the Temerty Faculty of Medicine at U of T. Gray-Owen is also the academic director of the Emerging and Pandemic Infections Consortium (EPIC) and the Toronto High Containment Facility.

“While it’s human nature to be reactive, we must strive to be proactive to prevent and limit the impact of future pandemics,” said Gommerman. “We need an approach that centres on co-operation, unity, a pooling of resources, a free and open sharing of data and a commitment to serve those most at risk – this is the Canadian way.”

Temerty Faculty of Medicine Professors Jen Gommerman and Scott Gray-Owen will co-lead the HI³hub (photos by Nick Iwanyshyn)

The HI³hub grew out of the lessons of the pandemic. The network will mobilize the resources of each partner in the collaboration, strengthening the country’s and Ontario’s biomanufacturing ecosystem and pandemic readiness.

Once fully operational, the hub will facilitate a rapid response network that will begin with identifying a new pathogen, developing diagnostics and treatments that can be manufactured domestically and working with public health authorities to engage the public and target at-risk populations where necessary.

The result? Faster, more equitable access to effective and tailored interventions, fewer people dying and suffering from long-term side effects of infection, and decreased social, economic and health system impacts.

“This investment from the federal government to establish the HI³ hub builds on the robust research and innovation ecosystem at U of T and on the strength of our partnerships across sectors,” said Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives. “By bringing together an unprecedented number of partners from universities, hospitals, industry and other fields, the hub is poised to expand and invigorate the innovation-to-product pipeline and protect the health of all people living in Canada.”

Precision interventions, process innovation and health intelligence

As one of five newly created hubs established with support from the Canada Biomedical Research Fund, HI³ partners/teams will compete for $570 million in research and infrastructure federal funding. The hub will enable high-risk, high-reward collaborative research projects focused on three themes: precision interventions such as vaccines and therapeutics; process innovations that leverage the power of AI to make biomanufacturing processes more streamlined and easier to implement in areas of need; and health intelligence, which pulls data from multiple sources to determine how well interventions work and guide the effective and equitable delivery of pandemic countermeasures.

The hub links industry and academic partners, including colleges, to create training opportunities and programs that attract, develop and retain the highly skilled workforce needed to drive innovation and growth in Canada’s biomanufacturing and life sciences sector.

Anchoring the hub at U of T means the significant expertise and infrastructure in life sciences research, advanced manufacturing, entrepreneurship and clinical care in the Greater Toronto Area and southern Ontario can be harnessed to make the hub a success. The Ontario region represents 47 per cent of Canadian pharmaceutical research and development expenditures and the Ontario pharmaceutical sector generates $43 billion in revenue.

“To continue to protect Canadians and to build a resilient biomanufacturing ecosystem, our government is taking every action possible to be equipped with the best tools. We’re proud to foster the research needed to produce cutting-edge discoveries and products in our very own labs that will help us build a stronger, more robust life sciences sector that responds to the needs of Canadians for decades to come,” said François-Philippe Champagne, minister of innovation, science and industry for Canada.

Funding for the HI³ is part of a larger investment in Canada’s Biomanufacturing and Life Sciences Strategy. The strategy aims to grow a strong, competitive domestic life sciences sector with cutting-edge biomanufacturing capabilities and to improve national pandemic preparedness. Through the strategy’s Biosciences Research Infrastructure Fund, U of T received $35 million in 2022 to revitalize the Toronto High Containment Facility, which played a pivotal role in accelerating research breakthroughs that guided the COVID-19 pandemic response in Ontario and Canada.

Among the hub’s major partners are six research hospitals from the Toronto Academic Health Sciences Network – Baycrest, the Hospital for Sick Children, Sinai Health, Sunnybrook Health Sciences Centre, Unity Health Toronto and University Health Network – and eight Ontario universities, including University of Guelph, Queen’s University, Toronto Metropolitan University, University of Waterloo, Western University, University of Windsor and York University.

In addition to its academic partners, the HI³ hub draws on the strengths of numerous major partners in industry and the public and not-for-profit sectors – adMare Bioinnovations, the Centre for Commercialization of Regenerative Medicine, CoVaRR-Net, Cyclica, Cytiva, the National Research Council of Canada, Providence Therapeutics, Resilience, Sanofi, Sartorius and the Vaccine and Infectious Disease Organization at the University of Saskatchewan.

The hub also leverages U of T’s experience in and capacity to support large-scale, high-impact interdisciplinary research, most notably through its Institutional Strategic Initiatives (ISI) program. Several ISIs – Acceleration Consortium, Centre for Research & Applications in Fluidic Technologies, Data Sciences Institute, Emerging and Pandemic Infections Consortium, Institute for Pandemics and Medicine by Design – are lending their expertise and providing support to help HI³ achieve its goals.

Clinical trial delivers chemotherapy to pediatric brain tumours using MRI-guided focused ultrasound

Christopher.Sorensen — Mon, 23 Jan 2023 19:42:20 +0000

Clinical trial delivers chemotherapy to pediatric brain tumours using MRI-guided focused ultrasound

Christopher.Sorensen Mon, 01/23/2023 - 14:42

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A brain scan shows an MRI-guided focused ultrasound opening the blood-brain barrier for delivery of chemotherapy to a common brain tumour in children (photo courtesy of Sunnybrook)

Jennifer Palisoc

Jessamine Luck

Topic

A team of Toronto researchers and physicians are the first in the world to use MRI-guided focused ultrasound to open the blood-brain barrier and deliver chemotherapy to treat Diffuse Intrinsic Pontine Glioma (DIPG), an aggressive and terminal pediatric brain tumour.

The first pediatric patient recently successfully underwent the procedure as part of a safety and feasibility clinical trial in children with this tumour.

A challenge for treatment of DIPG is the blood-brain barrier, a protective network of cells, which can prevent therapeutics from reaching areas in the brain. In this Phase 1 clinical trial, low-intensity focused ultrasound technology is used to temporarily open the blood-brain barrier with the power of soundwaves, allowing drug treatment to cross and treat the brain tumour.

“DIPG is a devastating pediatric brain tumour which is inoperable due to its location in the brainstem,” says Nir Lipsman, a neurosurgeon and director of the Harquail Centre for Neuromodulation at Sunnybrook Health Sciences Centre who is a co-principal investigator of the study. “Focused ultrasound is an innovative and non-invasive approach to more effectively delivering chemotherapy directly to the tumour. Our hope is that this continued research will bring us closer to enhancing treatments to help change the course of the disease.”

Lipsman is also an associate professor of surgery at the �ؿ�ζSM’s Temerty Faculty of Medicine.

The goal of the clinical trial is to safely and temporarily open the blood-brain barrier, a layer of cells, to deliver chemotherapy to the tumour with MRI-guided focused ultrasound (photo courtesy of Sunnybrook Health Sciences Centre)

“Current treatment for DIPG is limited to radiation, which can slow progression of the tumour for a period of time, but does not have longer-term effects,” says James Rutka, study co-principal investigator and director of the Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Chlidren (SickKids).

“Focused ultrasound technology is a promising drug-delivery strategy that is helping us penetrate the blood-brain barrier in a novel way,” adds Rutka, who is also a professor of surgery at Temerty Medicine. “Conducting this trial will help us build new and innovative treatment pathways for children with DIPG.”

DIPG tumours are the most common form of brain tumour in children under the age of 15 and make up nearly 10 to 15 per cent of all childhood brain tumours. It affects the region of the brainstem known as the pons, which regulates the body’s involuntary activities such as breathing, heart rate and important functions such as swallowing. DIPG is considered a terminal cancer.

Clinical and research teams from Sunnybrook and SickKids are collaborating on the clinical trial, which investigates the safety and feasibility of breaching the blood-brain barrier using MRI-guided focused ultrasound in combination with the delivery of chemotherapy in pediatric patients with DIPG.

Nir Lipsman, left, and James Rutka, right (photo courtesy of Sunnybrook)

The study includes 10 patients between five and 18 years old who have been diagnosed with DIPG. Study participants receive general anesthesia ahead of focused ultrasound treatment at Sunnybrook, which will involve three cycles of chemotherapy about four to six weeks apart. A specialized helmet is used to deliver ultrasound energy to brain targets without requiring scalpels or incisions. SickKids physicians and nurses will assist with the treatment procedure at Sunnybrook, and the children will receive post-operative care at SickKids.

Low-intensity ultrasound interacts with microscopic bubbles that vibrate causing a temporary opening in the blood-brain barrier, enabling therapies to pass and reach a targeted area. The blood brain barrier closes within hours of the procedure.

In 2015, Sunnybrook researchers were the first in the world to investigate low-intensity focused ultrasound in the opening of the blood-brain barrier and delivery of chemotherapy in adult brain cancer, and recently demonstrated in a trial that chemotherapy can be delivered across the blood brain barrier in brain metastases.

A team of researchers from Sunnybrook and SickKids monitor progress during treatment (photo courtesy of Sunnybrook)

Sunnybrook has also continued this leading-edge focused ultrasound research in other debilitating brain disease, including Parkinson’s disease, Alzheimer’s disease, Amyotrophic Lateral Sclerosis, major depression and other disorders.

This study was funded and supported by the Harquail family through the Harquail Centre for Neuromodulation; the Focused Ultrasound Foundation; and INSIGHTEC as well as by its lead donor at SickKids; Jordana’s Rainbows Foundation and the Fiorini family' Meagan’s Hug; Nelina’s Hope; and the Wiley family, who supported pre-clinical trial work.

This story originally appeared at the Hospital for Sick Children and Sunnybrook Health Sciences Centre.

Read a Q&A with the researchers in Maclean’s magazine

Class of diabetes drugs cuts dementia risk in older adults, research shows

lanthierj — Wed, 14 Dec 2022 17:52:21 +0000

Class of diabetes drugs cuts dementia risk in older adults, research shows

lanthierj Wed, 12/14/2022 - 12:52

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(photo by Yiu Yu Hoi/Getty Images)

Erin Howe

Topic

Diabetes

Graduate Students

A class of medication for Type 2 diabetes may help older people with the condition reduce their risk of dementia.

The findings are contained in a new study by Walter Swardfager, an assistant professor of pharmacology and toxicology at the Temerty Faculty of Medicine and a scientist in the Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Research Institute, and graduate student Che-Yuan (Joey) Wu.

Their research shows sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with a 20 per cent lower dementia risk when compared to another kind of medication known as dipeptidyl peptidase-4 inhibitors (DPP4).

Often, the first medication prescribed to people with Type 2 diabetes is metformin. When metformin alone doesn’t have the desired effect, additional therapies such as SGLT2 and DPP4 inhibitors, may be added or substituted. For many patients, physicians will choose between these two classes of drugs.

SGLT2 inhibitor medications, which include dapagliflozin and empagliflozin, are commonly prescribed. These drugs lower blood sugar by causing the kidneys to remove sugar from the body through urine. DPP4 inhibitor medications – which include linagliptin, saxagliptin and sitagliptin – work by blocking the action of an enzyme that destroys an insulin-producing hormone.

“The beautiful thing is that some diabetes medications, including the SGLT2 inhibitors, might manipulate the pathophysiology at an early stage before dementia develops,” says Swardfager. “We hope this strategy could prevent dementia for a group of people who are most vulnerable.”

From left: Walter Swardfager and Che-Yuan (Joey) Wu (photo by Erin Howe)

The study, published in the journal Diabetes Care, looked at more than 106,000 people aged 66 years and older. To make their observations, the researchers examined Ontario health records for people who were newly prescribed one of either kind of medication and who hadn’t previously experienced dementia. Then, they compared incidences of dementia between the two groups over a period of nearly three years.

They identified incident cases of dementia by hospitalization with a dementia-related diagnosis, three physician claims for dementia within a specified time frame, or by the prescription of a medication used to slow cognitive decline.

Though scientists don’t fully understand why, diabetes is known to increase a person’s risk of dementia, including vascular dementia and Alzheimer’s disease, by as much as two times.

The most common types of dementia involve deposits of abnormally folded proteins, as well as metabolic and vascular changes, in the brain.

Diabetes is known to damage blood vessels throughout the body, especially the small vessels, says Swardfager. The condition may also impair the brain’s smallest vessels.

“Under the current clinical guidelines, physicians have limited options to slow cognitive changes or lower the risk of dementia in people with diabetes,” says Wu. “Now, we have a potential candidate to help intervene in this process.”

The team next hopes to explore a newer class of diabetes drug called glucagon-like peptide-1 receptor agonists. Those drugs also have shown some promise for having brain benefits.

Wu and Swardfager hope to determine whether the benefits of particular drugs might be greater for certain individuals, and how this might contribute to personalized therapy or co-therapy with other medications to slow down dementia.

Swardfager is also excited by the potential for further studies that could help unlock some of dementia’s most complex mysteries.

“If we can give medications for diabetes early enough to protect the brain, it might have a real impact on an individual's trajectory,” says Swardfager. “Knowing which drugs show benefit may also offer new insights into how dementia begins and progresses in living people.”

This research was supported by funding from the Canadian Institute of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Alzheimer’s Association, Brain Canada, the Weston Brain Institute, Alzheimer’s UK, the Michael J. Fox Foundation and the Canada Research Chairs Program.

From Africana development to decarbonization: 34 U of T researchers awarded Canada Research Chairs

Christopher.Sorensen — Wed, 16 Nov 2022 19:01:13 +0000

From Africana development to decarbonization: 34 U of T researchers awarded Canada Research Chairs

Christopher.Sorensen Wed, 11/16/2022 - 14:01

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Scott Gray-Owen, Caroline Hossein and Marianne Hatzopoulou are three of 34 scholars at U of T who were awarded new or renewed Canada Research Chairs (photos by Nick Iwanyshyn, courtesy of Caroline Hossein, by Johnny Guatto)

Scott Anderson

Topic

Our Community

Leah Cowen

Donnelly Centre for Cellular & Biomolecular Research

Cell and Systems Biology

Institute of Health Policy Management and Evaluation

Astronomy & Astrophysics

Canada Research Chairs

Centre for Addiction and Mental Health

Computer Science

Dalla Lana School of Public Health

Faculty of Applied Science & Engineering

Faculty of Arts & Science

History

Ontario Institute for Studies in Education

Rotman School of Management

Sociology

U of T Scarborough

(See the full list of new and renewed Canada Research Chairs at U of T)

Thirty-four scholars at the �ؿ�ζSM have been awarded new or renewed Canada Research Chairs in fields ranging from artificial intelligence to health and history.

Many of the Canada Research Chairs are working on topics related to complex global challenges – advancing knowledge that will help accelerate the transition to clean energy, for example, achieve more equitable societies or develop new treatments for cancer and other debilitating diseases.

François-Philippe Champagne, Canada’s minister of innovation, science and industry, announced the chairs at the Canadian Science Policy Conference on Nov. 16, along with funding for a range of research programs and projects across the country – including the containment level 3 lab at U of T's Temerty Faculty of Medicine that enables researchers to study certain high-risk pathogens.

Among the 19 new chairs at U of T is Caroline Hossein, an associate professor in global development studies at U of T Scarborough. Named a tier two chair in Africana development and feminist political economy, Hossein studies “solidarity economies,” a movement that emphasizes social benefit over financial gain. She is writing a book about “rotating savings and credit associations” in Canada. These are small groups of immigrants, usually from Africa and the Caribbean, who often lack access to bank capital and come together to help each other financially.

Scott Gray-Owen, a U of T professor in the department of molecular genetics, was named a new tier one chair in infectious immunopathogenesis. His research aims to understand how pathogens such as bacteria and viruses infect their hosts and evade the immune response. In 2021, Gray-Owen was named the inaugural director of a new, forward-looking initiative at U of T called the Emerging and Pandemic Infections Consortium (EPIC), which seeks to combat new infectious diseases and prevent the rise of future pandemics. In that role, he also oversees U of T’s Combined Containment Level 3 Unit, a biosafety facility at the Temerty Faculty of Medicine that enables researchers to conduct research on certain pathogens.

How cities affect our health is the research interest of Marianne Hatzopoulou, a professor in the department of civil and mineral engineering in the Faculty of Applied Science & Engineering. She was named a new tier one chair in transport decarbonization and air quality. Hatzopoulou creates models of emissions from road transportation and evaluates how this air pollution affects the local population. Not long ago, she was involved in a study that used low-cost sensors to measure carbon monoxide, nitrogen dioxide, coarse particulate matter and other pollutants at nearly 70 sites across Beirut, identifying air pollution hot spots where people were most at risk. She also examined the effects of natural gas fracking in the northeast region of British Columbia. Another study examined the potential improvement in air quality resulting from the widespread adoption of electric vehicles.

Among the U of T faculty whose Canada Research Chairs were renewed is Jean Philippe Julien, senior scientist with the molecular research program of SickKids Research Institute and an associate professor in the department of biochemistry in the Temerty Faculty of Medicine. Julien also received support from the Canada Foundation for Innovation’s John R. Evans Leaders Fund (JELF), which helps provide research infrastructure associated with the Canada Research Chairs program, for his project, “Molecular Biological Systems for the Study of Antibody-Antigen Complexes.” Named for late U of T President Emeritus John R. Evans, the fund helps institutions recruit and retain outstanding researchers and provide them with the necessary tools and technology to perform their work.

“I’d like to commend all �ؿ�ζSM researchers who were named new Canada Research Chairs or who had their chair renewed in this latest round,” said Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives.

“The Canada Research Chair program provides critical support for researchers across our three campuses who are generating new knowledge, developing key innovations and helping to address some of the world’s most complex challenges.”

Established in 2000, the Canada Research Chair program invests up to $310 million annually to attract and retain top academic talent in disciplines spanning engineering, the natural sciences, health sciences, humanities and social sciences.

Here is the full list of new and renewed Canada Research Chairs at U of T:

New Canada Research Chairs

Aimy Bazylak in the department of mechanical and industrial engineering in the Faculty of Applied Science & Engineering, Tier 1 in clean energy.

Denise Belsham in the department of physiology in the Temerty Faculty of Medicine, Tier 1 in neuroendocrinology.

Maged Goubran at the Sunnybrook Health Science Centre and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in artificial intelligence and computational neuroscience.

Scott Gray-Owen in the department of molecular genetics in the Temerty Faculty of Medicine, Tier 1 in infectious immunopathogenesis.

Robin Hayeems at the Hospital for Sick Children and the Institute of Health Policy, Management and Evaluation in the Dalla Lana School of Public Health, Tier 2 in genomics and health policy.

Marianne Hatzopoulou in the department of civil and mineral engineering in the Faculty of Applied Science & Engineering, Tier 1 in transport decarbonization and air quality.

Caroline Hossein in the department of global development studies at U of T Scarborough, Tier 2 in Africana development and feminist political economy.

Muhammad Husain at the Centre for Addiction and Mental Health and the department of psychiatry in the Temerty Faculty of Medicine, Tier 2 in treatment innovation in mood disorders.

Courtney Jones at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in leukemia stem cell metabolism.

Andrea Knight at the Hospital for Sick Children and the department of paediatrics in the Temerty Faculty of Medicine, Tier 2 in mental health and chronic disease of childhood.

Sushant Kumar at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in genomic medicine.

J. Rafael Montenegro Burke in the Donnelly Centre in the Temerty Faculty of Medicine, Tier 2 in functional metabolomics and lipidomics.

Deborah O'Connor in the department of nutritional sciences in the Temerty Faculty of Medicine, Tier 1 in human milk and infant nutrition.

Vijay Ramaswamy at the Hospital for Sick Children and the department of paediatrics in the Temerty Faculty of Medicine, Tier 2 in pediatric neuro-oncology.

Gregory Schwartz at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in bioinformatics and computational Biology.

Jay Shaw in the department of physical therapy in the Temerty Faculty of Medicine, Tier 2 in responsible health innovation.

Anastasia Tikhonova at the University Health Network and the department of medical biophysics in the Temerty Faculty of Medicine, Tier 2 in stem cell niche biology.

Burton Yang at Sunnybrook Health Sciences Centre and the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine, Tier 1 in cardiac remodeling.

Darren Yuen at Unity Health Toronto and the department of medicine in the Temerty Faculty of Medicine, Tier 2 in fibrotic injury.

Renewed Canada Research Chairs

John Calarco in the department of cell and systems biology in the Faculty of Arts & Science, Tier 2 in neuronal RNA biology.

Myron Cybulsky at the University Health Network and the department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine, Tier 1 in arterial wall biology and atherogenesis.

David Duvenaud in the department of computer science in the Faculty of Arts & Science, Tier 2 in generative models.

Julie Forman-Kay in the Hospital for Sick Children and the department of biochemistry in the Temerty Faculty of Medicine, Tier 1 in intrinsically disordered proteins.

Bryan Gaensler in the David A. Dunlap department of astronomy and astrophysics in the Faculty of Arts & Science, Tier 1 in radio astronomy.

Alec Jacobson in the department of computer science in the Faculty of Arts & Science, Tier 2 in geometry processing.

Jean-Philippe Julien at the Hospital for Sick Children and the department of biochemistry in the Temerty Faculty of Medicine, Tier 2 in structural immunology.

Kang Lee in the department of applied psychology and human development at the Ontario Institute for Studies in Education, Tier 1 in moral development and developmental neuroscience.

David Levin in the department of computer science in the Faculty of Arts & Science, Tier 2 in simulation-driven graphics and fabrication.

Jed Meltzer at Baycrest Hospital and the department of psychology in the Faculty of Arts & Science, Tier 2 in interventional cognitive neuroscience.

Sean Mills in the department of history in the Faculty of Arts & Science, Tier 2 in Canadian and transnational history.

Kimberly Pernell-Gallagher in the department of sociology in the Faculty of Arts & Science, Tier 2 in economic sociology.

Arun Ramchandran in the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering, Tier 2 in engineered soft materials and interfaces.

Andras Tilcsik at the Rotman School of Management, Tier 2 in strategy, organizations, and society.

Haley Wyatt in the department of biochemistry in the Temerty Faculty of Medicine, Tier 2 in mechanisms of genome instability.

U of T receives $35 million to modernize high containment facility

Christopher.Sorensen — Wed, 16 Nov 2022 16:57:07 +0000

U of T receives $35 million to modernize high containment facility

Christopher.Sorensen Wed, 11/16/2022 - 11:57

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The Toronto High Containment Facility houses the largest containment level 3 lab in Ontario, where researchers can study high-risk pathogens such as SARS-CoV-2, HIV and the bacteria that causes tuberculosis (photo by Nathan Cyprys)

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COVID-19

Leah Cowen

The �ؿ�ζSM has received $35 million in critical research infrastructure funding from the federal government to revitalize the Toronto High Containment Facility (THCF), an investment that positions the facility to play a significant role in addressing future pandemic and health threats in Ontario and Canada.

The investment, which comes from the Canada Foundation for Innovation’s (CFI) Biosciences Research Infrastructure Fund (BRIF), is the largest CFI grant U of T has received to date and will support the university’s $85-million plan to modernize the 20-year-old facility.

Investments from other stakeholders – including the provincial government, hospital partners and philanthropists – are needed to ensure the successful completion of the critical project. Bringing together academic, hospital, industry and government partners, the modernized THCF will also provide space to research teams from U of T’s three campuses and other universities including Guelph, Queen’s, Toronto Metropolitan and York.

The funding support was announced by François-Philippe Champagne, minister of innovation, science and industry, at the annual Canadian Science Policy Conference in Ottawa. Across Canada, eight biosciences lab facilities at Canadian universities received funding.

"This investment, guided by the Biomanufacturing and Life Sciences Strategy, will help build Canada’s talent pipeline and research systems to grow a competitive domestic life sciences sector, with cutting-edge biomanufacturing capabilities,” Champagne said.

Based at the Temerty Faculty of Medicine, the THCF houses the largest containment level 3 lab in the province. It is equipped to allow researchers to study high-risk pathogens, such as SARS-CoV-2, HIV and the bacteria that causes tuberculosis, in a safe and secure way. The facility is also a cornerstone of the Emerging and Pandemic Infections Consortium (EPIC), a U of T institutional strategic initiative and collaboration between U of T and its hospital partners in the Toronto Academic Health Sciences Network (TAHSN) to drive innovative approaches to infectious diseases and prepare for future pandemics.

"This groundbreaking investment in the THCF will strengthen our ecosystem of collaboration and enable researchers at U of T and our partner hospitals to get ahead of future pandemics,” said Scott Gray-Owen, academic director of the THCF and EPIC, and a professor of molecular genetics in U of T’s Temerty Faculty of Medicine.

“It will empower our research community to address key questions and take discoveries through the innovation pipeline – from fundamental research to preclinical testing – accelerating progress that will benefit people in Canada and around the world.”

During the COVID-19 pandemic, the THCF played a critical role in accelerating key research breakthroughs that guided the pandemic response in Ontario and Canada – including becoming the first lab in Canada, and among the first in the world, to isolate the new coronavirus in March 2020. It completed research for the Public Health Agency of Canada, Bank of Canada, Royal Canadian Mint and Ontario Human Milk Bank, validating methods to allow safe reuse of personal protective equipment in health-care settings and ensuring safe human milk banking for premature babies throughout the pandemic, among other projects. The lab also supported academic projects to track new viral variants and understand transmission dynamics, as well as industry-led research efforts to develop new vaccines, drug candidates and immunotherapies that are currently being tested in clinical trials. Industry partners supported include: Edesa Biotech, I3 BioMedical and Providence Therapeutics.

“The federal government's support of the Toronto High Containment Facility through the BRIF recognizes the critical role this facility, its researchers and our hospital partners are playing in protecting Canada's health security,” said Leah Cowen, U of T’s vice-president, research and innovation, and strategic initiatives. “This is an important investment in critical infrastructure that will assist our talent and research to develop home-grown therapies and products that will protect Canadians' well-being."

The facility ran 24-7 during the pandemic as researchers pivoted their work from existing infectious diseases such as HIV and tuberculosis to deal with the new and urgent threat. The new federal investment will assist the facility to grow and be able to respond quickly to new threats while maintaining ongoing research projects.

Once complete, the updated lab space will provide increased research capacity to study a greater variety of emerging and re-emerging pathogens and allow it to take on new projects during a pandemic without compromising its ongoing work. It will also offer more opportunities to train the next generation of infectious disease leaders since training in operations and regulatory requirements at the facility mirror the manufacturing practice requirements for biopharmaceuticals and biomanufacturing. That, in turn, strengthens the talent pipeline to drive innovation and manufacturing in Ontario.

With 55 per cent of Canada’s pharmaceutical companies located in the greater Toronto area, the investment will further enhance the capacity of the life sciences ecosystem in the region to draw industry partners.

U of T and its hospital partners are already considered an engine of entrepreneurship in the health and life sciences in the region. They have helped create more than 200 startups over the past decade and are engaged in industrial partnerships valued at more than $100 million annually. This past spring, Moderna signed a partnership with U of T to prevent and treat infectious diseases.

The investment supports efforts to revitalize and expand THCF, transforming it into the largest high-containment academic research centre in Canada. The THCF renewal will be undertaken in collaboration with U of T’s hospital partners: The Hospital for Sick Children, Sinai Health, Sunnybrook Health Sciences Centre, Unity Health Toronto and University Health Network.

Researchers identify SARS-CoV-2 variant in white-tailed deer, evidence of deer-to-human transmission

Christopher.Sorensen — Mon, 14 Nov 2022 15:10:07 +0000

Researchers identify SARS-CoV-2 variant in white-tailed deer, evidence of deer-to-human transmission

Christopher.Sorensen Mon, 11/14/2022 - 10:10

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(Photo by Acton Crawford/Unsplash)

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COVID-19