On October 13-15, the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) organized a fully digital experience to showcase recent updates in multiple sclerosis (MS) research. The digital congress convened over 9,000 participants from 100 countries and offered a highly diverse scientific programme which covered topics on clinical aspects of MS, disease pathogenesis, biomarkers, and therapies in development. Below are some highlights of the cutting-edge research presented by clinicians and scientists.
Dr. Alan Thompson (University College London) was the recipient of the prestigious 2021 Charcot Award, which recognizes a lifetime achievement in outstanding research into understanding and treating MS. Over the course of his 40-year career, Dr. Thompson made tremendous impact on many areas of MS research and clinical care and improving the quality of life of people with MS, particularly those affected by progressive forms of the disease. In the following video, Dr. Thompson delivers the Charcot Lecture where he presents a personal perspective on research advances in progressive MS.
Dr. Hardeep Kataria (University of Manitoba) showed new data on the mechanisms by which Neuregulin-1, a critical protein for neural cells and myelin in the central nervous system, can foster myelin repair and axon preservation in progressive MS. Previous studies from Dr. Soheila Karimi’s group reported reduced levels of Neuregulin-1 protein in demyelinating lesions of mice with MS-like disease (i.e., experimental autoimmune encephalomyelitis or EAE mice). Interestingly, by providing Neuregulin-1 as a therapy, it was able to delay disease onset and alleviate disease progression and neurological impairment in EAE mice. In this new study, they showed that Neuregulin-1 promotes remyelination by modulating specific processes of microglia and macrophages within demyelinating lesions (i.e., phagocytic activity, lipid metabolism), and in turn creating a more suitable environment for oligodendrocyte differentiation, maturation and remyelination. Future research will need to test the effect of Neuregulin-1 in humans to see if the same results are found and if this could be a potential treatment for remyelination in MS.
Therapies in Development
A poster presentation by Dr. Patrick Vermersch (Lille University) reported new data from the Phase 3 EXPAND clinical trial, where they examined the effects of siponimod (Mayzent) on neurodegeneration in people with secondary progressive MS (SPMS). Siponimod is a selective sphingosine 1-phosphate receptor modulator indicated for the treatment of people with active SPMS as evidenced by relapses or imaging features. In this trial, researchers found that patients treated with siponimod showed preserved retinal thickness, a marker of neurodegeneration, compared to the placebo group at 12 months (change from baseline: 0.66 vs -1.86, respectively). Although this sub-study was conducted in a relatively small number of participants (N=104 in siponimod group; N=55 in placebo), the results correlate with previously observed beneficial effects of siponimod on other outcomes related to neurodegeneration (i.e., grey matter atrophy). Siponimod has been approved in Canada for active SPMS but additional data such as this may help expand the indication to include non-active SPMS.
Dr. Lawrence Steinman (Standford University) presented expanded results from two identical Phase 3 studies, ULTIMATE 1 and ULTIMATE 2, which are testing the efficacy and safety of ublituximab in people with relapsing MS compared with teriflunomide (Aubagio). Ublituximab is an anti-CD20 monoclonal antibody that targets and removes potentially harmful B cells in the blood and central nervous system of people with MS. Dr. Steinman reported that ublituximab met the primary end point for both ULTIMATE trials, and significantly reduced the annualized relapse rate (49-59% decrease) and MRI parameters (96% decrease in contrast enhancing T1 lesions and 90% decrease in new/enlarging T2 lesions) compared with teriflunomide in people with relapsing MS over a 96-week period. Furthermore, ublituximab was well-tolerated by study participants with no serious adverse events reported. The study investigators are expected to release additional data on the effects of ublituximab on cognitive impairment and brain volume metrics. The favourable efficacy and safety results of the ULTIMATE trials demonstrate the potential use of ublituximab as the first shortened dosing anti-CD20 infusion (1 hour infusion vs current 3+ hour infusions) in people with relapsing MS.
Biosensors in MS
How can we use modern day technology to help address unmet needs in MS clinical care? Researchers discussed the potential use of digital biosensors to support classical neurological exams, measure functional impairment, and predict progression in people with MS. A biosensor is a digital device that converts physical or biological events (e.g., gait, total number of steps, time duration per step) into a measurable signal. Accelerometers and heart rate monitors are among some of the commonly used biosensors that have been incorporated in smartphones and commercially available wearable devices (i.e., fitness trackers, smart watches), but whether these biosensing devices can be used in the context of MS is under investigation.
Dr. Tanuja Chitnis (Harvard University) presented findings from her recent work on a wearable smart watch sensor called Verily in patients with MS. Results from this trial found that biosensor readings taken at home were significantly correlated with clinical measures of disability, suggesting that this device could help capture information on MS symptoms and function in real-life settings (i.e., outside the clinic) and help physicians monitor patients in between clinic visits and potentially improve predictions about some disease outcomes.
COVID-19 and MS
Key learnings from the ongoing global pandemic were discussed by a panel of international experts. According to Dr. Maria Pia Sormani (University of Genoa), analysis of several COVID-19 and MS registries data showed that the risk of experiencing severe COVID-19 infection was correlated with the use of anti-CD20 therapies such as ocrelizumab and rituximab. In fact, the risk for more severe COVID-19 outcomes was higher with prolonged treatment. Additionally, interferon therapies may play a more protective role against COVID-19 infection and were associated with a lower risk for severe outcomes.
Dr. Renaud Du Pasquier (Université de Lausanne) also summarized recent findings on neurological complications associated with COVID-19 infection. He indicated that there is little evidence to suggest that the SARS-CoV-2 virus, which causes COVID-19, can physically penetrate the central nervous system and cause neurological effects. Instead, current data suggests that SARS-CoV-2 may likely trigger a dysregulated immune response that impairs blood-brain barrier function among COVID-19 patients.
For resources on COVID-19 and MS, please refer to the MS Society of Canada’s COVID-19 information page.
These are just some of the interesting new developments in MS research. To browse the full online program and presentation abstracts, please click here.