Location: Pavillon Ferdinand-Vandry (VND), 1050 Rue de la Médecine Room: VDN 1550

Move to Location: Pavillon Ferdinand-Vandry (VND), 1050 Rue de la Médecine Room: VND 2291A

Lead: Dr. Manu RangachariLocation: Pavillon Ferdinand-Vandry (VND), 1050 Rue de la Médecine Room: VND 2291A

Location: VND 2291A 8:30 - 9:15 am: Animal models of MS and the role of T cells (1h15) Moderator: Dr. Manu Rangachari 8:30 - 9:15 am Animal models of MS and introduction to T cells - Dr. Manu Rangachari (45 mins)Animal models of CNS autoimmunity and demyelination will be described, with a particular focus on the experimental autoimmune encephalomyelitis (EAE) model of MS. 9:15 - 9:45 am: Making progress: Modeling progression using an Nr1h3 variant identified in families with primary progressive MS - Dr. Jacqueline Quandt Developing effective treatments for the progressive phase of MS is a major challenge because of our limited understanding of the biological processes driving progression, and the lack of preclinical models presenting the spectrum of progressive MS characteristics. To address this challenge, we have created constitutive and inducible knock-in mice harboring a nuclear receptor subfamily 1 group H member 3 (Nr1h3) missense mutation (R413Q) homologous to the NR1H3 mutation (R415Q) identified in 7 patients diagnosed with MS from two families. These patients present a highly debilitating and rapidly progressive clinical course, linking biological disruption of the NR1H3 pathways to the development of PPMS. The NR1 family of proteins are key regulators of macrophage function, controlling transcriptional programs involved in lipid/cholesterol homeostasis and inflammation. Given the role of NR1H3 and its targets in lipid transport and immune modulation, we aimed to define mechanisms driving MS risk, severity, and progression. The Nr1h3 model shows subtle myelin dysregulation, a more pathogenic T cell and myeloid phenotype, increased disability, neurodegeneration, and reduced ability to repair, elucidating key mechanisms underlying aggressive and progressive MS. Objectives: •To review evolving concepts and processes relevant to the pathophysiology of aggressive/ progressive MS •To present a novel preclinical model with translational relevance to progression in MS

Dr. Alexandre Prat

Evaluation: https://www.surveymonkey.com/r/June20Session1

Evaluation link: https://www.surveymonkey.com/r/June20CareerDev Participants: Dr. Manu Rangachari, Dr. David Gosselin, Dr. Jacqueline Quandt and Dr. Pamela Kanellis Location: VND 2291A The goal of this session is to present the funding opportunities for trainees that are available through MS Canada, and to discuss strategies and tips for writing a competitive funding application.

#1 - Group photo of endMS Summer School participants, presenters, mentors, etc. (everyone!)#2 - Group photo of endMS SPRINT participants and mentors Location: Jardin du Décanat, 2nd floor

Location: VDN 1550 and VDN 4553 (photo studio) Each trainees will be scheduled for a professional, individual, headshot photo of themselves.

Location: VND 2291A Please note this session will be recorded. Evaluation link for SPRINT team presentations: https://www.surveymonkey.com/r/SPRINTpresentations2023

To what extent do trials of digital health technologies for persons with MS consider usability principles during development and evaluation? SPRINT Team Presenters: Adam Groh, Fiona Tea, Colleen Lacey (15 min) SPRINT Mentor: Dr. Afolasade Fakolade 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.

Moving Towards Better Outcomes: The Neuroprotective Role of Exercise in Multiple Sclerosis SPRINT Team Presenters: Syamala Buragadda, Karine Thai, Gracious Kasheke (15 min) SPRINT Mentor: Dr. Timothy KennedyCurrently, 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.

Investigating differences in fluid biomarkers between progressive MS subtypes SPRINT Team Presenters: Dr. Haritha Desu, Dr. Katherine Sawicka, Emily Wuerch (15 min) SPRINT Mentor: Dr. Jacqueline QuandtMultiple 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.

Evaluation Link for afternoon workshops: https://www.surveymonkey.com/r/June20PMWorkshops

Location: VND 1831 and VND 1853 Demystifying bioinformatics: introduction to RNA-seq analysis in R- Félix Distéfano-Gagné (30 min) Start with Group A VND 1831This workshop aims to demystify bioinformatic analysis. Students will first be briefly familiarized with the different steps downstream of RNA-sequencing. Then, through a guided example, students will perform a basic differential expression analysis using their own computer. Overall, this will provide students with the tools necessary to conduct and analyze their own RNA-seq experiments. (suggested background reading) Love et al, Genome Biol, 2014 (doi: 10.1186/s13059-014-0550-8) [method used for differential expression analysis]. Machado Xavier et al, bioRxiv, 2022 (doi: 10.1101/2022.08.04.502805) [preprint, source of provided datasets] Demystifying genome editing - Jacques P Tremblay (30 min) Start with Group B VND 1853 The workshop will present the CRISPR/Cas9 technology and the Prime editing technology derived from the CRISPR/Cas9. The Prime editing technology permits to replace any targeted nucleotide by the desired nucleotide. This technology may permit to correct point mutation responsible for thousands of hereditary diseases.

Demystifying human ethics approval and informed consent Nathalie Arbour (30 min) Start with Group A VND 1831 Objectives : -Develop an informed consent form: biobank, clinical and personal data, questionnaire, connected objects -Complete the different steps for human ethics approval: one-center vs. multicentric studies -Recruit participants successfully -Maintain privacy/confidentiality Taking into account our unconscious biases to foster inclusive work and research environments Geneviève Lapointe and Catherine Talbot-Bercier (30min) Start with Group B VND 1853Through various examples and interactive activities, this workshop aims to raise awareness regarding our unconscious biases and to understand their impacts on our work and research environments. After presenting different types of biases and their consequences, we will discuss how to adopt inclusive behaviours in our daily activities.

Shuttle bus will leave by 5:30pm from the Residence Pavillon Agathe-Lacerte, 1100, avenue de la Médecine Space is limited for trainees and those who confirmed in advance.

Trainees and presenters/mentors who confirmed attendance, should meet by the parking lot of Residence Pavillon Agathe-Lacerte, 1100, avenue de la Médecine at 5:15pm to travel via city bus (leaving by 5:30 pm) to bring group to the city centre to start the guided walking tour. Group A will be guided by JeanGroup B will be guided by Margarita