Canada's High Burden of Multiple Sclerosis and the Push for Advanced Research

Canada faces one of the highest rates of multiple sclerosis (MS) in the world, with over 90,000 individuals living with the condition, affecting approximately 1 in 400 people. This prevalence translates to nearly 4,400 new diagnoses annually, making MS a significant public health challenge. Universities across the country, particularly those with strong neuroscience programs, are at the forefront of efforts to understand and combat the disease. Institutions like the University of Toronto have emerged as leaders, leveraging cutting-edge imaging technologies to uncover hidden aspects of MS pathology that traditional methods overlook.

Synaptic loss—the degeneration of connections between neurons—plays a critical role in MS progression, contributing to cognitive decline, motor impairments, and long-term disability. While demyelination, the loss of the protective myelin sheath around nerves, has long been the hallmark of MS, emerging evidence highlights synaptic dysfunction as an early and pervasive feature. Canadian researchers are pioneering non-invasive tools to quantify this loss, paving the way for better diagnostics and therapies.

The Science Behind Synaptic Loss in Multiple Sclerosis

Multiple sclerosis is a chronic autoimmune disease where the immune system attacks the central nervous system, leading to inflammation, demyelination, and neurodegeneration. Synapses, the junctions where neurons communicate, are vital for brain function. In MS, synaptic loss occurs even in normal-appearing white matter and gray matter regions, correlating strongly with clinical disability scores like the Expanded Disability Status Scale (EDSS).

Step-by-step, the process unfolds as follows: immune-mediated inflammation triggers microglial activation, releasing excitotoxic glutamate and cytokines that damage synapses. Over time, this leads to reduced synaptic density, impairing neural circuits responsible for memory, movement, and cognition. Post-mortem studies confirm up to 30-50% synaptic reduction in advanced MS brains, but measuring this in living patients has been challenging until recent advances in neuroimaging.

At Canadian universities, such as the University of Toronto, faculty and students are dissecting these mechanisms through interdisciplinary collaborations in pharmacology, radiology, and neurology.

Introducing SV2A PET Imaging: A Breakthrough Tool for Synaptic Density

Synaptic Vesicle Glycoprotein 2A (SV2A) is a protein abundant in synaptic vesicles, making it an ideal target for positron emission tomography (PET) imaging. PET tracers like [18F]SynVesT-1 and [11C]UCB-J bind specifically to SV2A, allowing quantification of synaptic density non-invasively. The process involves injecting the radiolabeled tracer, which crosses the blood-brain barrier, followed by PET scanning to measure uptake and binding potential.

This technology offers superior sensitivity over MRI, detecting subtle changes in synaptic integrity across the brain and spinal cord. Developed through radiochemistry innovations, SV2A PET has been validated in Alzheimer's and epilepsy, and now extends to MS.

University of Toronto's Landmark Study on SV2A PET in MS

Led by Assistant Professor Dr. Chao Zheng at the University of Toronto's Temerty Faculty of Medicine, in the Department of Pharmacology and Toxicology and affiliated with the Centre for Addiction and Mental Health (CAMH), a recent study published in the Proceedings of the National Academy of Sciences (PNAS) demonstrates SV2A PET's efficacy in MS. The team used [18F]SynVesT-1 in experimental autoimmune encephalomyelitis (EAE) mice—a standard MS model—and [11C]UCB-J in a pilot human cohort.

In EAE mice, dynamic PET imaging revealed a nearly 30% global reduction in tracer distribution volume (VT) across all brain regions (P < 0.0001), with autoradiography confirming losses in the cervical and lumbar spinal cord. In six MS patients versus matched controls, global cortical SV2A binding dropped by 16.4% (P = 0.026), with 16-26% regional declines.Read the full PNAS study here.

Detailed Findings: Quantifying Synaptic Pathology Across Brain and Spine

The U of T study provides compelling evidence of widespread synaptic degeneration. In mice, PET scans showed uniform VT reductions, validated by immunofluorescence staining for SV2A protein. Human data mirrored this, with pronounced losses in cortical areas linked to cognition and motor control, independent of lesion load.

• Global brain VT decrease: ~30% in EAE model
• Human cortical binding: 16.4% lower in MS
• Spinal cord involvement: Confirmed via ex vivo analysis
• Correlation: Synaptic loss tied to disability progression

These results position SV2A PET as a translational biomarker, bridging preclinical models to clinical application.

Implications for Diagnosing and Monitoring MS Progression

SV2A PET addresses a critical gap: while MRI detects lesions, it misses diffuse synaptic loss driving irreversible disability. This tool enables early detection, tracking treatment responses (e.g., to disease-modifying therapies like ocrelizumab), and patient stratification for trials. In Canada, where MS prevalence peaks in prairie provinces due to genetic and environmental factors like low vitamin D, such imaging could personalize care.

Dr. Zheng notes, “We want to build tools that let us see what is happening inside the brain in a much more precise way,” highlighting its potential for hospitals nationwide.Explore U of T's feature on Dr. Zheng.

Dr. Chao Zheng's Lab: Fostering Innovation at U of T

Dr. Zheng, who joined U of T in 2023 after Yale, leads a dynamic lab synthesizing novel radioligands. Funded by CIHR grants (e.g., CIHR507113), his work exemplifies Canada's investment in brain health research. Collaborators from Yale and CAMH underscore interdisciplinary excellence at Temerty Faculty.

Students and postdocs in his lab gain hands-on experience in radiochemistry, PET analysis, and neuroscience, preparing them for academia or industry. U of T's Cyclotron/PET Centre supports such translational projects, positioning Toronto as a hub for neuroimaging.

Canada's Vibrant MS Research Ecosystem

Beyond U of T, universities like University of Alberta's MS Centre ($16.5M CIHR funding), Dalhousie ($2M for health outcomes), and Memorial University ($1.15M molecular MS) drive progress. CIHR and MS Society of Canada fund over $10M annually, supporting biomarkers, genetics, and therapies.

This network fosters multi-site trials, leveraging Canada's diverse MS population for robust data.

Future Outlook: Transforming MS Care with Synaptic Imaging

Ongoing trials will test SV2A PET in larger MS cohorts, evaluating neuroprotective drugs. Advances in tracer longevity (e.g., fluorine-18) enable wider clinical use. Canadian researchers aim to integrate this into routine monitoring, potentially slowing progression and improving quality of life.

As Dr. Zheng emphasizes, translating lab tools to clinics “makes me really happy,” signaling a bright future for MS patients.

Photo by Harman Tatla on Unsplash

Career Opportunities in Canadian Neuroscience Research

The demand for experts in neuroimaging and MS research is surging at Canadian universities. Roles in pharmacology, radiology, and data analysis abound, with competitive salaries and CIHR funding support. Institutions like U of T seek postdocs, lecturers, and professors to advance synaptic imaging.

• Research Assistantships: Hands-on PET experience
• Faculty Positions: Lead innovative labs
• Clinical Trials Coordinators: Bridge research to patients

This field offers impactful careers addressing Canada's MS epidemic.