Research We Fund

Characterizing the neuroprotective roles of bHLH proteins Npas4 and ARNT2 in inflammatory neurodegeneration related to multiple sclerosis

Summary: In multiple sclerosis (MS), damage to nerve fibers and death of neurons occurs in the brain and spinal cord. The molecules regulating this destruction in MS are unknown. The research team will: Evaluate how two molecules, previously identified to play a role in damage to nerve fibers and death... Read the full article

Molecular mechanisms underlying T cell/oligodendrocyte interactions as target for neuroprotective strategies in MS

Summary: Myelin, the covering on the nerve fibers destroyed by immune cells in multiple sclerosis (MS), is provided by cells in the brain and spinal cord called oligodendrocytes. The interactions between immune cells and oligodendrocytes are unknown and there is a need to better understand this interaction... Read the full article

Defining a dual role for VGF in the regulation of MS pathology

Summary: VGF is a molecule that is induced during exercise and is shown to increase myelination. VGF also promotes the maturation of myelin-producing cells called oligodendrocytes. VGF interacts with macrophages/microglia- immune cells that can be both detrimental and beneficial in multiple sclerosis... Read the full article

Targeting DICAM, a novel mediator of neuroinflammation, to treat MS

Summary: The blood-brain barrier (BBB) is a network of cells that line all the blood vessels in the brain, preventing harmful substances such as bacteria and toxins from entering the brain and spinal cord. The BBB is compromised and becomes leaky in multiple sclerosis (MS), allowing white blood cells... Read the full article

Inflammasome activation in the central nervous system: determinants and outcomes in progressive MS

Summary: Inflammasomes are protein complexes in the immune system that are activated by infection. These complexes are also activated in multiple sclerosis (MS) and promote inflammation and brain injury. The factors regulating inflammasomes in progressive MS are unclear. The research team will: Identify... Read the full article

Elucidating the role and regulation of astrocytes in multiple sclerosis

Summary: High levels of the protein Cystatin C is found in the brains of individuals with multiple sclerosis (MS) and early research has shown that increasing Cystatin C is detrimental in animal models of MS. How Cystatin C emits is negative effects in MS is unknown. The research team will: Examine... Read the full article

Investigating a novel inhibitory signaling mechanism that represses T cell-driven CNS autoimmunity

Summary: Serpine1 is a protein that has been shown to reduce damage to the myelin caused by the harmful T cells from the immune system in an animal that mimics multiple sclerosis (MS)-like disease. How Serpine1 exhibits its function on MS is unknown. The research team will: Examine proteins that are... Read the full article

Impact of IL-27 on MS pathobiology

Summary: IL-27 is a molecule that can diminish the severity of multiple sclerosis (MS) in a mouse model of the disease. Whether IL-27 is beneficial in individuals with MS is unresolved. The research team will: Compare the impact of IL-27 on immune cells from people with MS compared to those from healthy... Read the full article

Immune cell influences on neuronal viability and repair

Summary: microRNAs are molecules which have been implicated in regulating neurons in response to inflammatory stimuli. They have the ability to silence the expression of many genes at once. Whether microRNAs can silence many genes that prevent nerve cell repair simultaneously is unknown. The research... Read the full article

Immune cell-microbiome interactions and neuroinflammation

Summary: One type of immune cell, call the B cell, can have either anti- or pro-inflammatory properties. The function of the B cell is also thought to be influenced by microbes in the gut microbiome. B cells function is believed to be compromised in multiple sclerosis (MS) and how the gut microbiome... Read the full article

Targeting novel functions of cysteine cathepsins to limit neuroinflammation

Summary: During inflammation, molecules called cytokines are released by immune cells and these molecules are used to communicate with other immune cells, guiding them to the damaged brain cells and bringing more immune cells into the brain. One major cytokines that causes inflammation and damage to... Read the full article

Targeting Oligodendrocyte Maturation for the Study of Axonal Survival

Summary: One hallmark of multiple sclerosis(MS) is that the nerve cell processes lose their surrounding insulation material, called myelin, leading to a greater risk of demyelination and neurodegeneration. MYRF is a molecule that is downregulated in MS lesions of humans. It has also been shown to promote... Read the full article

Novel strategies to enhance intrinsic repair following demyelination

Summary: Electrical stimulation and intermittent reduction of oxygen in the spinal cord of injured animals enhances the inherent ability of the nervous system to repair itself. Whether these two methods would be beneficial in multiple sclerosis (MS) is unknown. The research team will: Use models of... Read the full article

Circadian control of pain and neuroinflammation in experimental autoimmune encephalomyelitis

Summary: Chronic pain, impacting more than 50% of individuals with multiple sclerosis (MS), is associated with inflammation in the brain and spinal cord in MS as well circadian (24-hour) rhythms. Early research has identified a role for circadian rhythms in disease progression in MS, however, whether... Read the full article

The Role of Antibody-Secreting Cells in MS/EAE

Summary: B cells have a dual role in multiple sclerosis (MS). A subset of B cells slow the disease course in MS while another subset have detrimental effects on MS. The gut microbiome is the richest source of B cells. The role of a subset of B cells, called plasma cells, found in the gut microbiome... Read the full article

Elevated axonal and myelin injury with aging: Mechanisms, prevention and prospective therapeutics for progressive multiple sclerosis

Summary: Age is a key factor associated with progression from relapsing to progressive forms of multiple sclerosis (MS). Destructive oxygen radicals are activated in MS and may play a role in age-dependent injury. How they are activated and cause injury is unknown. The research team will: Examine aging-enhanced... Read the full article

A New Mouse Model Linking Degeneration with Inflammation to study Multiple Sclerosis

Summary: This research aims to explore how MS is initiated and hypothesizes that MS starts as a degenerative disorder and then leads to an aggressive autoimmune attack against nerve fibers in the brain resulting in inflammatory ‘plaque’. To test this hypothesis, the group has developed a new animal... Read the full article

FKN as a novel remyelination agent: at the interface of cell-to-cell interactions

Summary: Myelin is a fatty substance that protects nerve cells and acts to enhance their signal transmission. MS results from abnormal activity of the immune system whereby the body’s own immune cells target and damage myelin and myelin-producing cells called oligodendrocytes located in the central... Read the full article

The Interleukin-1 Cytokine System as a Target for the Treatment of Multiple Sclerosis

Summary: The molecule, interleukin (IL)-1ß, has been identified as a key messenger involved in the development and severity of central nervous system autoimmunity. IL-1ß may be acting like a key that opens the door to the central nervous system, allowing entry of aggressive immune cells in to the brain... Read the full article

Impact of MicroRNA-223 on Immune and Glial Cells in Multiple Sclerosis

Summary: While microRNAs are found in both immune cells and brain cells, some can play an important role in controlling inflammation and tissue repair in the damaged brain. One microRNA in particular, called mir-223, may be important in promoting the brain to repair itself. However, in MS this microRNA... Read the full article

Deciphering Astrocyte - T cell interactions in Multiple Sclerosis

Summar y: This research aims to understand astrocytes, a type of cell found in the brain named for their star-like appearance and investigates their conribution to MS disease processes and progression. Astrocytes are the most abundant cell types in the central nervous system (CNS) and are known to respond... Read the full article

Sex and Central Nervous System Autoimmunity

Affiliation: Toronto General Research Institute  Summary: One of the top risk factors for multiple sclerosis (MS) development is being female. Women outnumber men with this disease by 3-fold, and the reason is still unknown. There is a need to better understand the fundamental biological differences... Read the full article

Role of neutrophils as antigen-presenting cells in autoimmune demyelination

Summary: Neutrophils are white blood cells that are part of the immune system and are involved in the demyelination that occurs in multiple sclerosis (MS). The mechanism of action through which neutrophils contribute to damage in MS is unknown. The research team will: Characterize the expression of... Read the full article

Identifying New Molecular Mechanisms that Promote Myelin Maintenance and Remyelination

Principal Investigator: Dr. Timothy Kennedy Summary: Myelin is the protective covering around nerve fibers that is damaged in multiple sclerosis (MS). Researchers are actively looking for cellular molecules that regulate the production and repair of myelin in conditions such as MS. Netrin-1 is a molecule... Read the full article

Targeting Programs of Gene Expression to Enhance Neuroprotection

Background: Many of the current treatments for multiple sclerosis (MS) modulate the immune system and are generally ineffective at treating progressive forms of the disease. Nerve cell degeneration and death in the brain and spinal cord underlie progressive forms of the disease and disability in MS, Read the full article

Enhancing Microglial Myelin Repair Mechanisms through Stimulation of the Ppar-Delta Nuclear Receptor as a Novel Therapeutic Approach for Multiple Sclerosis

Background: Myelin, the protective coating surrounding nerve fibres, is necessary for the transmission of nerve impulses in the body. In people with multiple sclerosis (MS), the immune system attacks myelin, causing inflammation and often damaging the myelin coating. The brain possesses the capacity... Read the full article

Predicting Disease Deterioration in Multiple Sclerosis

Background: A current limitation in multiple sclerosis (MS) care is the ability to accurately predict whether a person’s MS will worsen and when, since the disease trajectory differs for each individual with MS. Being able to better predict a person’s disease trajectory can influence the healthcare... Read the full article

Therapeutic Effects of Mir-145-5p Antagonism in a Mouse Model of Multiple Sclerosis

Background: Multiple Sclerosis (MS) is a disease in which the insulation around the nerve fibres, known as myelin, becomes damaged by the immune system. This damage can result in loss of muscle control and partial paralysis. Oligodendrocytes are a specialized cell type that produce myelin sheaths around... Read the full article

Characterizing Inflammatory and Neurodegenerative Pathways Driving Clinical Disease in Primary Progressive Multiple Sclerosis

Background: To develop more effective treatments for multiple sclerosis (MS), researchers require a better understanding of the biological processes that lead to susceptibility and progression, as well as animal models that emulate human disease. Unlike relapsing-remitting MS, progressive MS is not... Read the full article

Defining the Role of Unconventionally Activated Meningeal B Cells in CNS Autoimmune Inflammation

Background: With the development of new disease modifying therapies that target immune system cells called ‘B cells,’ it has become increasingly important to better understand the role of B cells in multiple sclerosis (MS). While we understand that B cells are important drivers of MS pathology, its... Read the full article

Sex Chromosomes Dictate T Cell (Th17) Pathogenicity

Background: A person’s sex is an important, yet complex factor in the development and progression of multiple sclerosis (MS). Current evidence indicates that 75% of people in Canada living with MS are women - women are three times more likely to develop MS than men, while men with MS progress more rapidly... Read the full article

Characterization of a Novel Dendritic Cell-specific Protein in Demyelinating Autoimmune Diseases

Summary: Autoreactive immune cells called T cells play a central role in diseases such as multiple sclerosis (MS) and MS-like animal models (EAE mouse model). To perform their role, T cell activity is regulated by dendritic cells (DC). Recently, the team found a novel cell-surface protein of unknown... Read the full article

Hierarchy of Inhibitors in the Lesion Microenvironment for Remyelination: Combining a Novel CNS-Targeting Therapeutic with Exercise to Promote Repair

Summary: MS results from abnormal activity of the immune system whereby the body’s own immune cells target and damage myelin (the outer protective coating of nerve fibers) and myelin-producing cells called oligodendrocytes located in the central nervous system. Regeneration of oligodendrocytes and subsequent... Read the full article

MicroRNA-mediated Regulation of Inflammasome Activity in Multiple Sclerosis

Summary: There is a need to find new and effective drugs that will stop MS disease progression. Recent research has implicated a protein structure called the ‘inflammasome’, a group of proteins that assemble within the brains of MS patients and significantly contributes to both inflammation and cell... Read the full article

Targeting T Cell Metabolism to Reduce Neuroinflammation in Multiple Sclerosis

Summary:  Western diet, obesity and related comordities are risk factors for MS onset and progression. Scientific evidence shows that restricting intake of methionine, an essential amino acid found in high-levels in meat-based diets, is associated with a prolonged lifespan (anti-aging), slower cancer... Read the full article

Deciphering the Influence of Epstein-Barr Virus in Multiple Sclerosis

Summary: The goal of the research is to better understand the role of Epstein-Barr Virus (EBV) in the development and progression of MS. EBV is a common virus that infects people in childhood or early adulthood and remains quiet (causes a latent EBV infection) in our immune system. Project Description:... Read the full article

Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo)

Summary: One of the unmet needs is a better understanding of, and treatment options for, progression in MS. While current therapies in MS aim to slow the progression of the disease, there are no treatment options that successfully alter the trajectory of progression. A key to altering progression in... Read the full article