METFORMIN IN CHILDREN WITH MS

We want to see if we can repair damaged myelin in children with MS using a drug called metformin. Previous research has shown that metformin helps repair myelin in mice and may associate with decreased relapses in adults with MS and metabolic syndromes.

If interested please contact Tara Berenbaum (416-813-7654 x328576 or tara.berenbaum@sickkids.ca)

Damage to white matter in the brain occurs in MS, and results in sensory, motor, and cognitive problems. Multiple disease modifying therapies are available, including therapies that provide good control of inflammatory disease activity, but do not reverse the progressive nature of the disease. Importantly, the current standard of care includes only therapies that target inflammatory factors related to the disease; approaching the disease from a reparative perspective may have additional benefits.

Currently, while there is much research focused on repair and remyelination, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In the proposed research, we hope to change this situation by enhancing the creation of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the creation of oligodendrocytes from neural precursors and that, following pediatric white matter injury, this promotes structural and functional recovery.

The use of metformin represents a highly innovative strategy to treat youth with MS. Finding a low-cost strategy may be of great benefit both to society and individuals with MS. This early phase trial will produce essential preliminary evidence for safety and tolerability of this approach.

In this study, participants will take metformin for either 3, 6, or 9 months depending on which group they are randomly assigned to. Participation will be for a total of 12 months and will require 5 visits to SickKids.

Positive results in our clinical trial will lead to a dramatic shift in how we treat youth with multiple sclerosis, and will pave the way for future additional clinical trials in children and adults with multiple sclerosis.

If interested please contact Tara Berenbaum (416-813-7654 x328576 or tara.berenbaum@sickkids.ca)

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VISUAL OUTCOMES IN NEUROINFLAMMATION

There are multiple studies underway to identify measures of central nervous system structure and function most sensitive to neuroinflammatory disorders, with a particular focus on the visual system.

We are performing multiple studies evaluating the visual system in neuroinflammatory disorders. These observational studies specifically focus on early structural and functional manifestations of optic neuritis and longitudinal changes in the visual pathway and visual function in youth with neuroinflammatory disorders.

Together, these studies will allow us to identify the most sensitive measures as readouts of the structural and functional effects of neuroinflammation for use in future research. Finally, we are performing studies evaluating the relationship between visual outcomes, eye movements (using eye tracking), and neural oscillations (using MEG).

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OPSOCLONUS-MYOCLONUS-ATAXIA SYNDROME (OMAS)

The goal of this study is to investigate eye movement outcomes in relation to brain volume, cognitive function, and disease severity in pediatric OMAS.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare but serious autoimmune neurological illness that typically affects toddlers and young children. Neuroblastoma (a tumour of the sympathetic nervous system) is found in up to 50% of paediatric OMAS cases, and 2-3% of children with neuroblastoma will develop OMAS. Symptoms of OMAS include uncontrolled rapid eye movements (opsoclonus), involuntary jerking of muscles (myoclonus), body coordination/balance difficulties (ataxia), and behavioural/sleep disturbances. Even with treatment, a large proportion of children with OMAS continue to experience long-term cognitive, behavioural and motor deficits; however, early intervention has been shown to improve prognosis in some cases. The complexity of the disease combined with the lack of standardized diagnostic testing and assessment tools pose major challenges for timely diagnosis and management of OMAS. The goal of our research is to investigate eye movement outcomes in relation to cerebellar volume, cognitive function, and disease severity in paediatric OMAS. Findings from this study will help contribute to the development of standardized assessment tools for outcome evaluation in OMAS.
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NEURAL OSCILLATIONS AND COGNITIVE DYSFUNCTION IN MS

The purpose of this study is to get a better understanding of physical measures, specifically brain structure and brain waves, that are linked to problems in brain functioning, such as speed of thinking, that happen shortly after a patient is diagnosed with MS.

The purpose of this study is to get a better understanding of physical measures, specifically brain structure and brain waves, that are linked to problems in brain functioning, such as speed of thinking, that happen shortly after a patient is diagnosed with MS. This is important because these brain waves can help us find possible treatments to help fix the brain structure that could be causing the problems with brain functioning in patients with MS. In this study, we will focus on the brain waves since they seem to move differently in patients with MS compared to healthy children.
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