endMS National Training Program
Here are the summaries of the 2022-2023 SPRINT team projects:
Investigating differences in fluid biomarkers between progressive MS subtypes
SPRINTers: Dr. Haritha Desu, Dr. Katherine Sawicka, Emily Wuerch
SPRINT mentor: Dr. Jacqueline Quandt
SPRINT team project presentation description: Multiple sclerosis has largely been divided into three main clinical subtypes: relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive (PPMS). While RRMS is most common initially and characterized by episodes of clinical worsening followed by remission, progressive MS is typified by continuous worsening without remission. Most patients with RRMS will transition to SPMS around the fifth decade of life, similar to the age of onset for the smaller percentage who are diagnosed with PPMS from onset. While great advances have been made in the treatment of RRMS, our knowledge of the pathobiology underlying progressive MS is lacking. For instance, it is currently unclear whether SPMS and PPMS represent a similar disease with different patterns of onset but comparable pathological processes, or if they represent largely separate manifestations with varying contributions of inflammatory or reparative processes to each. This has led to a lack of standard regarding whether progressive patients should be grouped together, or if more can be learned through evaluation/distinction as different groups in clinical studies or trials. Our objective was to conduct a rapid literature review of markers associated with neuroaxonal or glial degenerative processes examined in fluid biomarkers studies, with the goal of identifying whether or not differences exist between PPMS and SPMS. This work will inform the design of future studies to address the underlying pathophysiology of progressive MS by highlighting biomarkers with similarities or differences between progressive MS subtypes.
Lay Summary: Multiple sclerosis (MS) is a long-term disease that happens when myelin, the protective layer around nerve fibres, is attacked by the body’s own immune system. This attack makes it difficult for the brain to send signals to the rest of the body, and can lead to brain cell damage. Depending on the area that is affected, MS can lead to problems with vision, movement, sensation, thinking, and fatigue. ​To help patients, doctors, and researchers understand the disease course and help make treatment decisions, three types of MS have been described: ‘relapsing remitting’, ‘primary progressive’, and ‘secondary progressive’. ‘Relapsing remitting’ MS means symptoms come and go with recovery in between. 'Primary progressive’ MS means symptoms never go away and continually worsen. ‘Secondary progressive’ MS means symptoms start in a relapsing pattern, but switch to a progressive course later in life. While scientists have been steadily improving their understanding of these different types of MS, many questions remain. Our research question focused on finding differences in blood and brain fluid between people described as having ‘primary progressive’ or ‘secondary progressive’ MS. Understanding these differences may help researchers develop better therapies for treating worsening symptoms and/or the progression of the disease. To answer this question, we carefully looked at previous studies measuring markers of brain damage in people MS, and compared results between people with ‘primary progressive’ or ‘secondary progressive’ MS. We found that most studies combined participants with ‘primary’ and ‘secondary progressive’ MS together as one group, making it hard to identify the differences between them. A better understanding of the differences that may or may not exist between these groups should be a focus for future research, as it will help provide more information and guidance on how to best treat persons with worsening MS.
Moving Towards Better Outcomes in Multiple Sclerosis
SPRINTers: Syamala Buragadda, Karine Thai, Gracious Kasheke
SPRINT mentor: Dr. Timothy Kennedy
SPRINT Team Project Presentation Description: Currently, most therapies in MS target the immune system by preventing leukocytes to infiltrate the central nervous system (CNS) and cause new lesions. However, they do not act efficiently to promote repair and remyelination in existing lesions, which results ultimately in disability progression. Increasing evidence supports a role for exercise in the improvement of neurological status in people with MS by promoting neuroplasticity. The purpose of this presentation is to underline the relationships between pharmacological and physical approaches that show promise in promoting remyelination in MS. We will provide an overview of the immunological processes that lead to impaired remyelination in this disease and discuss how these can be mitigated to promote remyelination and neuroprotection. We focus on exercise as an intervention with potential to provide clinical benefits for individuals with MS.
Lay Summary: In multiple sclerosis (MS), white blood cells invade the brain and inappropriately attack the insulating layer around nerves. This layer is called "myelin" and helps speed nerve transmissions. Most MS therapies prevent white blood cells from entering the brain and causing new lesions. However, they come with possible side effects and do not all effectively promote the repair of existing lesions, which may result in disability progression. Exercise is a safe intervention that can improve the neurological status of many individuals with MS. Both aerobic and strength exercises can benefit individuals with MS, yet the precise mechanisms remain less understood. Exercise induces favorable changes in brain blood vessels, immune function, and neurological processes. Here, we address the biological mechanisms triggered by exercise and how they may provide tangible benefits for individuals with MS. Outside of the brain, exercise can improve vascular health and immune function. Better vascular health means that blood vessels become less permeable and do not allow white blood cells to exit the bloodstream and enter the brain. In addition, the autoimmune response and the capacity of immune cells to migrate are decreased. This can limit the entry of white blood cells into the brain. Inside the brain, exercise promotes repair after immune attacks. Repair occurs by the creation of myelin from new cells and from injured but recovering cells. Damaged cells that are unable to recover are eliminated to create an environment favorable for the creation of new myelin. This can promote recovery after relapses and decrease the rate of progression caused by the loss of neuronal cells. Current literature suggests that various forms of exercise may limit brain damage by white blood cells and increase brain repair mechanisms in MS. Exercise can thus be seen as a safe intervention to be prescribed alongside current disease-modifying therapies.
To what extent do trials of digital health technologies for persons with MS consider usability principles during development and evaluation?
SPRINTers: Adam Groh, Fiona Tea, Colleen Lacey
SPRINT Mentor: Dr. Afolasade Fakolade
Lay Summary: In recent years, the use of digital health technologies (DHTs), such as mobile apps and wearable devices, has increased in managing MS. Our research explored how easy and practical (i.e., usability) DHTs are for people with MS. We sought to explore the types of available digital tools, their characteristics, and how their usability is measured in DHT research for people with MS. We searched several research databases for studies published since 2010 and found that usability was considered in less than a third of studies, indicating a limited focus on the user experience when evaluating DHTs. Most studies measuring usability focused on mobile apps. However, there was a general lack of consistency in how researchers measured usability, making it difficult to provide a clear summary of how user-friendly these tools are. Our research highlights how important it is to involve people with MS in developing and evaluating DHTs. Studies must do a better job at systematically determining how user-friendly these tools are so that they can be easy for everyone with MS to use, regardless of their background or symptom severity.  We recommend a user-centered approach in future DHT development, which includes:  (1) Exploring aspects of DHTs that matter to people with MS, including user needs, satisfaction, and accessibility. (2) Using consistent approaches to evaluate usability across studies, such as questionnaires and interviews.   (3) Tailoring to the specific type of DHT, needs, and expectations of the person with MS. For instance, for wearable devices, it is useful to know how long they can be comfortably worn. For apps that involve completing tasks, it is helpful to see how long it takes.
SPRINT Team Project Presentation Description: The objective of our scoping review was to map the literature discussing usability characteristics during the design and evaluations of digital health technologies (DHTs) for persons with multiple sclerosis (MS). DHTs (e.g., wearables, mobile applications, assessment platforms, etc.) are becoming substantially more integrated into the long-term care of persons with MS. DHTs offer complementary and alternative methods to track and manage symptoms, improve treatment adherence, and increase access to healthcare for persons affected by MS. In order to ensure that DHTs meet the end-user’s needs and are adopted into long-term care, it is essential to incorporate usability characteristics into the design and evaluation of these tools. The current talk will outline how DHTs targeting the MS population incorporate usability characteristics in their design and evaluation.