A University of Toronto (U of T) based research team, co-led by Dr. Jennifer Gommerman from U of T's Temerty Faculty of Medicine and Dr. Valeria Ramaglia from U of T and UHN’s Krembil Brain Institute, has discovered how progressive multiple sclerosis (MS) develops. Their findings also point to a promising biomarker—a measurable biological sign of disease—that could help clinicians better identify, and eventually treat, individuals living with this debilitating form of the disease.
Progressive MS is notoriously difficult to diagnose and treat because its underlying inflammation occurs deep within the brain and is challenging to measure in living patients. The findings of this study offer a way to better understand this hidden process and determine which patients are most likely to benefit from current or emerging therapies.
MS is a degenerative autoimmune disease. An autoimmune disease occurs when the immune system attacks healthy cells or tissues. In the case of MS, it attacks myelin—the protective insulation surrounding nerve fibres in the grey matter of the central nervous system (CNS), including the brain and spinal cord. This damage disrupts neuron-to-neuron communication and leads to symptoms such as muscle weakness, vision problems, pain, and changes in mood or behaviour. In progressive MS, these symptoms worsen over time, leading to increasing disability.
MS is characterized by “compartmentalized” inflammation, which occurs when the immune response that causes inflammation moves from the surrounding tissues to specific compartments of the CNS. In progressive MS, inflammation has been observed in the meninges—the thin, protective layers that surround the CNS. This inflammation can lead to the formation of small lymph node-like structures made of clusters of immune cells, including B cells, in the meninges.
Although previous studies have linked meningeal lymph node-like structures to grey matter injury in progressive MS, the mechanism connecting them remained unclear.
“To close this knowledge gap, we recognized we needed to innovate,” says Dr. Ramaglia. “Utilizing a novel lab model that accurately reproduced the grey matter injury seen in progressive MS was an essential first step."
Using their new model, developed at U of T, the team examined how immune proteins behave during grey matter injury. The results revealed striking changes in two immune proteins: CXCL13 and BAFF, proteins that help control immune cells. At the onset of injury, CXCL13 increased by 800-fold, while BAFF levels decreased significantly.
When the team introduced a Bruton’s tyrosine kinase inhibitor (BTKi)—a drug that blocks the BTK protein, which mediates immune cell activity—the effects of brain injury were reversed: CXCL13 decreased and BAFF increased, restoring a ratio of CXCL13:BAFF comparable to that seen in uninjured models. BTKi treatment also reduced both the number and size of lymph node-like structures in the meninges. Together, these results revealed that meningeal inflammation and grey matter injury are driven by a balance of CXCL13 and BAFF and depend on BTK signalling.
These discoveries led the researchers to propose that the CXCL13:BAFF ratio could serve as a biomarker for meningeal inflammation and possibly compartmentalized inflammation deeper in the brain. To test their hypothesis, the Gommerman-Ramaglia team examined brain tissue samples from individuals with MS. They found that patients with a greater number of immune cells in the brain’s protective layers—indicating more severe inflammation—also had elevated CXCL13:BAFF ratios.
A separate analysis of MRI data from another patient group further supported this finding. Individuals with parametric rim lesions (PRLs), brain lesions that are another marker of progressive MS, also showed higher CXCL13:BAFF ratios compared to individuals without these lesions.
Although further studies are necessary, if validated, this ratio may give clinicians a practical tool to identify patients experiencing the type of inflammation associated with progressive MS.
By unravelling the circuitry that contributes to progressive MS, this research offers insights that could help shape future treatment strategies. It identifies possible new avenues for therapeutic development, as well as sheds light on factors that may explain why existing treatments have been less effective in progressive disease. The team also believes it could support recruitment for ongoing clinical trials of BTK inhibitors and help improve how patients who are most likely to respond to a treatment are identified.
“With Canada having one of the highest rates of MS worldwide, it seems fitting that this advancement in our understanding is homegrown”, notes Dr. Gommerman.
As she builds her own research program at Krembil Brain Institute, Dr. Ramaglia continues to collaborate with Dr. Gommerman to explore how the ratio could advance precision medicine in MS. Building on this study, Dr. Ramaglia plans to focus next on investigating whether the CXCL13:BAFF ratio can be used to help predict which individuals with early MS may go on to develop the progressive form of the disease. This could mean earlier diagnosis and better treatment options for people living with progressive MS.
Dr. Ramaglia credits Dr. Gommerman’s mentorship as instrumental to her growth as an independent scientist and helping to set her up for success as she transitioned to her new role as an independent Principal Investigator at Krembil Brain Institute.
*Check out the University of Toronto Temerty Faculty of Medicine’s feature on this work here.
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The first author of this study is Dr. Ikbel Naouar, a Senior Research Associate at the University of Toronto.
Drs. Valeria Ramaglia and Jennifer Gommerman are co-senior authors of this study. Dr. Ramaglia is a Scientist at UHN’s Krembil Brain Institute and an Assistant Professor of Immunology at the University of Toronto. Dr. Gommerman is a Professor of Immunology at the University of Toronto, and a Tier 1 Canada Research Chair in Tissue-Specific Immunity.
This work was supported by the National Multiple Sclerosis Society, MS Canada, the Canadian Institutes of Health Research, the United States Department of Defense, and UHN Foundation. Support from the National Multiple Sclerosis Society and the United States Department of Defense was given to Drs. Gommerman and Dr. Ramaglia. Support from MS Canada and the Canadian Institutes of Health Research was given to Dr. Gommerman.
Dr. Gommerman shares a patent for the treatment of autoimmune disease, such as multiple sclerosis, or inflammation, which includes at least the administration of B-cell activating factor (BAFF). Drs. Cenni and Nuesslein-Hildesheim are employees of Novartis. For a complete list of competing interests, see the publication.
Naouar I, Pangan A, Zuo M, Raza SA, Champagne-Jorgensen K, Patel J, Wang A, Pu A, Ward L, Ahn JSY, Sayeed FN, Zhu J, Pössnecker E, Cenni B, Nuesslein-Hildesheim B, Browning JL, Probste A-K, Reich DS, Gommerman JL*, Ramaglia V*. Lymphotoxin-dependent elevated meningeal 1 CXCL13:BAFF ratios drive grey matter injury. Nat Immunol.
Slipping on ice is a major cause of winter injuries and a costly burden to the Canadian health care system. A new study from UHN’s KITE Research Institute shows that even top-rated winter boots cannot fully prevent slips, highlighting the need for additional safety measures.
As winter footwear design advances, researchers at the KITE Research Institute WinterLab evaluate slip resistance using a standardized test to measure how well boot sole technologies reduce the risk of slips and falls. Using a specialized platform that recreates winter conditions, researchers developed the Maximum Achievable Angle (MAA) test, which measures the steepest slope an individual can walk on without slipping. This provides a clear measure of slip resistance, but ice remains unpredictable and uniquely hazardous compared to other surfaces.
To better understand slip risk on icy surfaces, the research team recruited 27 participants to walk on an icy walkway while wearing a safety harness and 11 different winter boot models from popular brands, including Timberland, Merrell, and WindRiver. Boots were categorized as poor, moderate, or good slip resistance based on their original MAA score.
The results were striking. Analyzing over 8,500 steps, researchers found that nearly 12% resulted in a slip—approximately one slip every nine steps. Boots with poor ratings had a 36% slip risk, while even the highest rated boots still showed a 4–5% slip risk. Even advanced designs could not fully prevent slips.
These findings highlight that ice remains far more hazardous than most surfaces. While choosing boots with higher slip-resistance ratings is important, additional measures such as timely ice clearing, heated pavements, and safer walking techniques are needed to reduce winter injury.
This research group provides slip-resistance testing of winter footwear for manufacturers. Insights may inform the design of future commercial or service-based applications.
Davood Dadkhah, first author of the study, is a PhD candidate at UHN’s KITE Research Institute in the lab of Dr. Tilak Dutta.
Dr. Tilak Dutta, senior author of the study, is a Senior Scientist at UHN’s KITE Research Institute. At the University of Toronto, Dr. Dutta is an Associate Professor in the Institute of Biomedical Engineering and the Institute of Rehabilitation Sciences.
This work was supported by the Natural Sciences and Engineering Research Council of Canada and UHN Foundation.
Dadkhah D, Ghomashchi H, Dutta T. Determining the risk of slipping on level ice using winter footwear with varied maximum achievable angle slip-resistance performance. Appl Ergon. 2026 Feb. doi: 10.1016/j.apergo.2025.104678. Epub 2025 Oct 31.
Retinitis pigmentosa (RP) is a degenerative eye disease that causes the progressive loss of photoreceptors—the light-sensitive cells in the retina—leading to vision loss and, eventually, blindness. Autosomal recessive RP is a form of the disease caused by genetic mutations, most commonly in the USH2A gene. This gene encodes Usherin, a protein that helps keep photoreceptors functional and healthy.
Until now, there was no reliable human disease lab model to study how USH2A-associated RP begins and progresses, which has slowed the development of new treatments. To address this gap, Dr. Brian Ballios and his team from UHN’s Donald K. Johnson Eye Institute (DKJEI) developed a retinal organoid model that more closely reflects USH2A-associated RP in the mature human retina. Organoids are 3D lab-grown models of a tissue or organ that capture the complex structure and function of real tissue.
To create these organoids, the team used induced pluripotent stem cells (iPSCs)—lab-made stem cells created by turning mature cells back into a state where they can become any type of cell again—using blood cells from patients with USH2A-associated retinitis pigmentosa. To compare to patient-derived organoids, the team also created organoids from healthy iPSCs that they genetically engineered to lack the gene. Throughout the organoids’ development, Dr. Ballios and the DKJEI team analyzed their genetic, molecular, cellular, and structural characteristics.
The findings show that retinal organoids with USH2A mutations are a good model, as they closely resemble what is seen in the clinic in individuals with RP. This includes the pattern of photoreceptor loss and changes to the retina’s structural and molecular characteristics that accompany the loss.
In addition, the study sheds light on how USH2A mutations drive changes in the development of the retina, contributing to photoreceptor loss in RP. For example, these models showed that fewer photoreceptors form in retinas with USH2A mutations, resulting in a smaller pool of photoreceptors that is lost more quickly. The research further highlighted the role of USH2A in early retinal development, which was previously unexplored. These changes happen long before symptoms appear, making them impossible to study without organoid models or in patients directly.
This work is an important step toward understanding retinitis pigmentosa. By offering a reliable model that can be manipulated in the lab, these findings could improve future research into new therapies. By beginning to understand the developmental underpinnings of USH2A-associated RP, this work may also introduce new avenues for early intervention aimed at slowing or preventing retinal degeneration. For patients, this progress moves us closer to a future where blindness is not inevitable in those living with retinitis pigmentosa.
Kristen Ashworth, Jiajie (Jackson) Zhang, and Cassandra D’Amata are co-first authors of this study. Kristen is a research trainee at UHN’s Donald K. Johnson Eye Institute (DKJEI) and a PhD candidate at the University of Toronto. Jiajie completed his MSc at the University of Toronto and is now a research technician in the Ballios Lab at DKJEI. Cassandra is a research technician and the lab manager of the Ballios Lab at DKJEI.
Dr. Brian Ballios, the senior author of this study, is a Scientist and a Retina Specialist at UHN’s Donald K. Johnson Eye Institute and an Assistant Professor at the University of Toronto’s Temerty Faculty of Medicine.
This work was supported by the Foundation Fighting Blindness, the University of Toronto, and UHN Foundation.
The authors report no competing interests.
Ashworth KE, Zhang J, D'Amata C, Héon E, Ballios BG. USH2A-Mutated Human Retinal Organoids Model Rod-Cone Dystrophy. Invest Ophthalmol Vis Sci. 2025 Nov 3;66(14):2. doi: 10.1167/iovs.66.14.2.
In a recent study published in Science Robotics, Dr. Pascal John Mosimann from UHN’s Krembil Brain Institute and his international team at the Swiss Polytechnic School in Lausanne (EPFL) developed a new catheter system that uses blood flow to reach very small brain blood vessels faster and more safely. This approach is the first to enable super-selective embolization—the delivery of a drug that blocks blood flow, called an embolic agent, to a targeted area—in vessels previously considered too small, deep, or tortuous for existing technologies.
Super-selective embolization involves guiding a very small catheter, called a microcatheter, through a blood vessel to deliver the embolic drug to a precise location, stopping blood flow. Until now, endovascular catheters could only be safely used in vessels a minimum of 0.5 millimetres (mm) wide—about as thick as a credit card—although many vessels requiring treatment measure 0.05–0.4 mm. Existing microcatheterization systems require physically pushing the catheter along the vessel walls, increasing the risk of vessel wall damage or perforation.
Using advanced engineering techniques, Dr. Mosimann and his team developed a new microcatheter system about as thin as a human hair called MagFlow. The system remains flat while it moves through the vessel and then inflates when a drug or other therapeutic agent is injected once it reaches the desired treatment location. MagFlow utilizes blood flow in the artery or capiliary that the catheter is in to move, eliminating the need for manual force and thus reducing the risk of injuring the blood vessel wall. A specialized external magnet, called OmniMag, can be moved around the outside of a patient’s head to assist with positioning of the catheter. Movement of the catheter is monitored via X-ray fluoroscopy.
Results from tests in preclinical models were promising. The novel MagFlow and OmniMag system could be safely and effectively guided and used for the injection of embolic drugs in vessels as small as only 0.18 millimetres—about as thin as a cat’s whisker.
This advancement could transform care for patients with aneurysms, strokes, brain tumours, and other complex vascular conditions. By enabling access to vessels previously considered unreachable, MagFlow opens the door to highly targeted therapies that minimize risk and maximize precision. Clinicians may soon be able to treat delicate brain regions with less trauma, offering safer interventions and expanding options for conditions that were once untreatable.
The first author of this study is Dr. Lucio Pancaldi, a former Postdoctoral Scientist at École polytechnique fédérale de Lausanne (EPFL) in Switzerland.
Dr. Pascal John Mosimann, a Clinician Investigator at UHN’s Krembil Brain Institute and Associate Professor of Neuroradiology at the University of Toronto’s Temerty Faculty of Medicine, and Dr. Mahmut Selman Sakar, an Associate Professor and director of the MicroBioRobotics Systems Laboratory at EPFL in Switzerland, are corresponding and senior co-authors of the study.
This work was supported by the European Research Council (ERC), Innosuisse, BRIDGE, Innogrant, the Swiss National Science Foundation, and UHN Foundation.
Drs. Pancaldi and Sakar filed patents for the ultraflexible flow-directed device and system, and another patent on the magnetic guide system.
Pancaldi L, Özelçi E, Gadiri MA, Raub J, Mosimann PJ, Sakar MS. Flow-driven magnetic microcatheter for superselective arterial embolization. Sci Robot. 2025 Oct 22;10(107):eadu4003. doi: 10.1126/scirobotics.adu4003.
MagFlow microcatheter device sitting on a gloved adult hand, to emphasize the size of this new technology. (Image courtesy of Dr. Pascal Mosimann)
Depression and anxiety are common following spinal cord injury (SCI) and can worsen pain and negatively impact quality of life. Researchers at UHN’s KITE Research Institute (KITE) are exploring how adapting the language and content of mindfulness-based interventions—programs that teach present-moment awareness and acceptance—can improve psychological well-being and recovery for individuals with SCI.
Mindfulness-based interventions are proven to reduce pain and improve mood in those with chronic pain. However, most interventions were designed for individuals without motor or sensory impairments. Standard exercises such as mindfulness walks or instructions like “feel your feet on the ground” can be frustrating or impossible for those with limited mobility or altered sensation. Without adaptation, these practices may feel inaccessible and discourage participation.
To explore how mindfulness-based interventions could be made more inclusive, KITE researchers interviewed 22 individuals with SCI to identify motivators and barriers to practicing mindfulness. Participants noted physical challenges—such as pain, stress, and poor sleep—as key motivators. They also reported perceived benefits, including reduced anxiety and depression, improved emotional regulation, and feeling more present in relationships.
Barriers included misconceptions about how hard it is to fit mindfulness into daily life and a lack of accessibility in the language used during exercises. Emphasis on specific body postures or traditional mindfulness practices, such as walking meditations, made participation challenging.
Adapting mindfulness-based interventions with more inclusive language, flexible options for body positioning, and improved education around mindfulness could greatly increase program accessibility. Removing these barriers could support more patient-centred care for individuals with SCI.
Dorothy Luong, first author of the study, is a Research Associate at UHN’s KITE Research Institute in the lab of Dr. Sarah Munce.
Dr. Sarah Munce, senior author of the study, is an Affiliate Scientist at UHN’s KITE Research Institute and an Implementation Scientist at the Holland Bloorview Kids Rehabilitation Hospital. At the University of Toronto, Dr. Munce is an Associate Professor at the Institute of Health Policy, Management, and Evaluation and is cross appointed at the Rehabilitation Sciences Institute.
This work was supported by Crain H. Neilsen Foundation and UHN Foundation.
Luong D, Lee TJ, Simpson R, Fetterly MJ, Jaglal S, Allin S, Craven C, Hearn J, Webster F, Munce S. How do individuals with spinal cord injury practice mindfulness? Barriers & facilitators to practicing mindfulness and considerations for tailoring programs. Disabil Rehabil. 2025 Oct 29. doi: 10.1080/09638288.2025.2580297. Epub ahead of print.
A new study from UHN unveils an AI model to analyze data from electrocardiograms (ECG)—quick, low-cost recordings of the heart’s electrical activity that are commonly used as an initial test for patients with cardiac symptoms. This model has been made publicly available and may enable faster, more consistent ECG interpretation for screening, assessing risks, and predicting the need for further testing—information that isn't readily available.
AI tools can help doctors interpret ECG results. However, most AI tools need large volumes of manually labelled data to learn general patterns. A foundation model—a type of AI trained on a very large dataset to learn patterns in the data—can get around this issue through its ability to learn the basic patterns in non-labelled ECGs. After that, it only needs a few labelled examples to work on new tasks.
A research team at UHN set out to create a publicly accessible foundation model capable of interpreting ECGs and assessing its performance on clinical tasks. Using data from 1.5 million ECG tests, they developed ECG-FM, a model designed to learn ECG patterns on its own. The team then evaluated its ability to interpret common ECG findings and predict changes in heart function indicators such as reduced left ventricular ejection fraction (LVEF)—an important measure of how effectively the heart pumps blood.
When tested, ECG-FM performed better than previous models and worked well across different datasets and with little labelled data. It was accurate in interpreting common ECG findings and identifying LVEF and heart rhythm irregularities such as atrial fibrillation.
Overall, ECG-FM is versatile, efficient, and accurate for tasks like heart screening, risk assessment, and monitoring and reduces the need for large, labelled datasets, providing a reproducible framework for ECG research. To support comparability and usage, the team has released their AI code along with tutorials and a public benchmark so that others can test, adapt, and improve it. This is especially beneficial for small ECG datasets geared toward a specific task. These details can be found here.
Kaden McKeen is a Doctoral Candidate in Dr. Bo Wang’s lab and the first and corresponding author of the study.
Dr. Sameer Masood is a Clinician Investigator at UHN and an Assistant Professor in the Department of Medicine at the University of Toronto. He is the clinical lead and co-author of this study.
Dr. Bo Wang is the Chief AI Scientist and a Senior Scientist at UHN, and an Associate Professor in the Departments of Laboratory Medicine & Pathology and Computer Science at the University of Toronto. He is the senior author of the study.
This work was supported by UHN Foundation.
McKeen K, Masood S, Toma A, Rubin B, Wang B. ECG-FM: an open electrocardiogram foundation model. JAMIA Open. 2025 Oct 16;8(5):ooaf122. doi: 10.1093/jamiaopen/ooaf122.
UHN has secured the top spot on the list of Canada’s Top 40 Research Hospitals by Research Infosource Inc. This marks the 15th consecutive year UHN has led the rankings, a testament to our commitment to advancing health research.
The annual rankings compare research hospitals across Canada based on research spending, including grants, contributions, and contracts from internal and external government and non-government sources. In the 2024 fiscal year, UHN invested over $599 million in research, reinforcing its position as a global leader in discovery and innovation.
Within the "Large Hospital" category (institutions with total hospital spending exceeding $1 billion), UHN also ranked among the top for research intensity—defined as the percentage of research spending relative to overall hospital expenditures.
Dr. Brad Wouters, UHN’s Executive Vice President of Science and Research, shared: “We are incredibly proud to be recognized as Canada’s top research hospital once again—a position that reflects the passion and contribution of the 6,000-plus members of our research community and the many supporters of this team. From novel discoveries to clinical innovation and education, we are united by one purpose: improving health and transforming care for patients everywhere.”
This short video celebrates the people, places, and passion driving UHN’s continued success as Canada’s top research hospital.
These achievements are supported by strong partnerships with many institutions, including our financial supporters—The Princess Margaret Cancer Foundation and UHN Foundation—government agencies, industry, and other charities. UHN is proud to be part of Toronto’s vibrant research ecosystem alongside the University of Toronto and other academic hospitals, working together to accelerate discovery and impact. We are also strongly supported by our many patient partners that work with us every day towards our goal to create A Healthier World.
Research Infosource Inc. reports on research activity across Canada. Click on the following links to view the complete list of Canada’s Top 40 Research Hospitals and a Spotlight on Hospital Research Activity within the Large Hospital category.
Research at UHN takes place across its research institutes, clinical programs, and collaborative centres. Each of these has specific areas of focus in human health and disease, and work together to advance shared areas of research interest. UHN's research spans the full breadth of the research pipeline, including basic, translational, clinical, policy, and education.
See some of our research areas below:
Research at UHN is conducted under the umbrella of the following research institutes. Click below to learn more:
