Myelin repair strategies, progressive MS, exercise, and other promising avenues took center stage at the virtual European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2021 meeting, with some 9,000 participants from 100 countries convening to share progress in understanding and treating MS.
Advances were reported from many different avenues of research, driving progress along Pathways to Cures
that will stop MS, restore function, and end MS by prevention. Below are a few highlights from the many important presentations, with links to their abstracts. Studies presented at scientific meetings are generally considered preliminary until they are published in peer-reviewed journals.
Many presenters shared results demonstrating continued benefits of available therapies, and longer-term safety data showing that early and ongoing treatment with a disease-modifying therapy has long-term benefits for controlling disease activity, delaying buildup of disabilities, and protecting quality of life. Several studies also reported on efforts to determine how to predict an individual’s disease course and progression to guide better treatment decisions.
Other studies reported on potential benefits of experimental therapies including “BTK inhibitors” (such as fenebrutinib, evobrutinib, tolebrutinib), which are in late-stage clinical trials in both progressive and relapsing MS. BTK inhibitors are thought to both reduce the activation of immune B cells that play a role in MS, and inhibit immune cells in the brain called microglia, which have been linked to MS progression.
“Progressive MS has moved to center stage,” noted Professor Alan Thompson, who gave the ECTRIMS Lecture as the recipient of the 2021 MSIF Charcot Award
. Understanding what drives chronic inflammation and nerve degeneration, and how aging plays a role, are key to stopping progression. Many presentations focused on the cause of tissue damage that might be targeted by new therapies in the not too distant future.
For example, the brain’s internal immune cells, called microglia, are the subject of intense investigation. These cells conduct important functions, including clearing away myelin debris to make way for myelin repair. But they can also go rogue and contribute to “smoldering” inflammation and nerve degeneration.
Stem cells for nerve protection:
- Dr. Dori Schafer (University of Massachusetts Medical School, Worcester) described how an immune mediator called complement can team up with microglia to snip nerve connections (synapses) and interrupt brain circuitry in MS. The team is are now working to understand the sources of complement molecules and determine how they regulate synapse loss and inflammatory activity in MS. (Abstract 110) This study adds to recently published data on the role of complement in MS.
- Dr. Anthony Chomyk (Cleveland Clinic) presented results showing that microglia, which are present on the borders of slowly expanding MS lesions, show different patterns of gene activation depending on which area of the brain the lesions are in. Identifying gene alterations in microglia from different brain areas could help to provide new targets for MS therapeutics. (Abstract 175)
Dr. Jeffrey Cohen (Cleveland Clinic) presented first results from a phase 2 open label clinical trial that tested a stem cell therapy (NurOwn®, Brainstorm Cell Therapeutics) on 18 people with primary progressive or secondary progressive MS. The cells were derived from individuals’ own bone marrow (mesenchymal) stem cells, which were treated in the laboratory to encourage them to secrete neuroprotective factors. The participants then received three separate cell treatments by injection into the spinal canal every two months. The treatment appeared to be safe (which was the primary purpose of the study), and there also appeared to be some improvements in cognition, vision, mobility, and other functions by comparing participants with those involved in other studies. A grant from the Society’s commercial investment program-Fast Forward provided funding to measure the levels of anti-inflammatory and neuroprotective substances in the spinal fluid as a potential way to quickly detect the biological activity of the treatment in future clinical trials. Biomarkers in spinal fluid suggested nerve protection and reduced inflammation. The company is determining next steps for developing this experimental approach for treating progressive MS. (Abstract 114
Comorbidities linked to brain volume changes:
There is increasing evidence that having MS along with other disorders (“comorbidities”) can worsen a person’s MS disease course and progression. There is also hope that managing their comorbidities will pay off in better outcomes for their MS. Dr. Kathryn Fitzgerald (Johns Hopkins University, Baltimore) and collaborators explored links between heart health-related comorbidities such as diabetes, high blood pressure, and high cholesterol and worsening of brain atrophy measures on MRI scans in over 3,000 people with MS. Nearly half had no comorbidities, and 18% had two or more. Those 18% tended to have significantly faster brain volume loss than those with no comorbidities. (Abstract 103
Learn more about managing MS along with comorbidities
Role of genes in relapse risk:
Over 230 gene variations have been uncovered that contribute to people’s risk of developing MS, but the role of gene variants in the disease course remains unclear. Dr. Marijne Vandebergh (University of Leuven, Belgium) and colleagues conducted a large gene study in nearly 1,000 people with relapsing MS before they began disease-modifying therapy to search for variants that might increase risk for MS relapses. Those carrying a rare variant (rs11871306 within WNT9B region) were twice as likely to relapse as those without it. More study, now underway, is needed to identify other variants related to disease severity and to understand how thee and other findings might pave the way for a more personalized approach to treatment. (Abstract 078
Sense of Smell and Therapy Response:
Alterations in a person’s sense of smell may be a common issue in MS and may represent a way to track underlying disease activity. In a study of 123 people with relapsing MS tracked over 5 years, Gabriel Bsteh, MD, PhD (Medical University Vienna) and colleagues tested whether smell sensitivity was linked to responses to treatment. When improvements in the ability to smell occurred in the first three months of starting disease-modifying treatment, participants were less likely to experience a relapse. If confirmed, sensitivity to odors could become an easily trackable marker of treatment response. (Abstract 085
) Read more about how smell and taste are affected by MS
This year’s ECTRIMS reflected the growing awareness that neurological conditions, including MS, are experienced differently among people of different races, ethnicities, and that socioeconomic factors can contribute to these differences.
Costs of MS:
- Dr. Maria Petracca (Icahn School of Medicine at Mount Sinai, New York) studied whether the aggressive disease course that has been reported in Black people with MS might be partly related to socioeconomic factors limiting access to care or influencing lifestyle choices. In fact, in this study of 60 Black people with MS and 60 white people, even in complex models accounting for socioeconomic factors, Black people had more severe disability status than white people. (Abstract P189)
- Dr. Mitzi Williams (Joi Life Wellness Group, Atlanta) studied disparities between patients and providers in the Black and white communities, surveying 27 providers, 182 Black people with MS and 28 white people with MS. The team identified important differences in responses. For example, preventing disability progression was a top goal for Black and white people (74% and 86%, respectively) but for only 54% of providers. Most providers (76%) reported discussing clinical trials, but 65% of Black people and 29% of white people reported not discussing trials. Importantly, 50% of Black people with MS reported that discrimination was a barrier to care, versus 34% of providers and 19% of white people. (Abstract P235) Learn more about MS in the Black community
- Dr. Justin Abbatemarco (Cleveland Clinic) and colleagues used the Area Deprivation Index, which identifies the least and most disadvantaged neighborhoods, to look at links with clinical measures and quality of life in nearly 2,000 people with MS. People with MS living in the most disadvantaged neighborhoods had worsening in most outcomes. The team is hoping to compare data with MRI results in the future and include information on other factors such as lifestyle habits. (Abstract 102) Find resources for financial struggles.
Dr. Bruce Bebo (National Multiple Sclerosis Society, USA) presented some of the findings from a Society supported study focused on estimating the total economic burden of MS in the United States. The study found that the average annual cost per individual living with MS is $65,463, and the total cost for all individuals with MS is $85.3 billion. Medications and healthcare are a significant burden, along with unpaid caregiving, lost earnings, and other costs. Detailed results will be published in a peer-reviewed journal, and will help support advocacy for better access to high quality healthcare, better caregiver support, and other important services needed for people affected by MS. (Abstract 163
Preserving and repairing myelin is likely to be one of the best ways we can prevent nerve degeneration and allow the nervous system to restore connections and restore lost function. Several ECTRIMS presentations focused on potential myelin repair strategies, and creative new rehabilitation strategies and symptom management techniques to maximize abilities and to treat troubling symptoms and restore function.
While disappointing results were presented from phase 2 clinical trials of experimental nervous system repair approaches (opicinumab Abstract 147
and elezanumab Abstract 149
), there were positive findings and plans presented for moving forward. In an invited talk reviewing the topic, Dr. Catherine Lubetzki (Sorbonne University, Paris) described promising new targets and approaches like calorie restriction to overcome aging and stimulate repair processes in people with MS. (Abstract 108
Dr. Amit Bar-Or (University of Pennsylvania, Philadelphia) and colleagues presented updated outcomes from an extension study of a phase 1/2 clinical trial of experimental ATA188 (Atara Biotherapeutics) in progressive MS, which uses immune T cells to target the Epstein-Barr virus (EBV), considered a risk factor for developing MS. The team reported that a proportion of participants in the open-label extension of this study showed a reversal of disability, and those with more improvement also showed increases in a brain imaging signal (MTR) thought to represent myelin repair. The next phase of this trial is underway. (Abstract P638
Proof of concept for experimental repair therapy:
One possibility being explored in the failure of the brain to keep up with MS damage is the availability of energy within cells. Dr. Robert Glanzman (Clene Nanomedicine, Holladay, Utah) presented results of a study to determine if people with MS being treated with the company’s experimental therapy Biocatalytic Nanocrystalline Gold (CNM-Au8) showed improvements in energy metabolism. He showed indicators that indeed the compound can provide supportive energy to brain cells. A trial is underway in Australia to determine whether this compound improves MS disease activity by facilitating myelin repair and by protecting brain cells from damage. Through Fast Forward, the National MS Society is providing funding to measure and track blood markers in trial participants to help determine if the compound is helping. (Abstract 150
Exercise – early and late in MS:
Reducing leg spasms long term:
- Drs. Morten Riemenschneider and Ulrik Dalgas (Aarhus University, Denmark) highlighted research on exercise in MS. “Some of us are starting to believe that exercise is actually medicine in multiple sclerosis,” said Dr. Dalgas, who noted that a review of exercise studies cumulatively exhibited a large beneficial effect on quality of life. “Disability level and disease duration did not influence the effects, indicating that it’s never too late to improve your life through exercise.” (Abstract 141)
- Dr. Riemenschneider reported on a study of people early in the course of MS, which they are undertaking based on evidence in mouse models that exercise may protect against MS development. Among 84 people with relapsing-remitting MS diagnosed in last two years, there was no difference in those completing an aerobic exercise program in terms of relapses and brain tissue volume as those completing a health education program. However, close examination revealed evidence that exercise had neuroprotective effects on certain regions of the brain. (Abstract 143) Further study is warranted to understand the true potential of exercise in MS, but guidelines are available for all.
Dr. Rainer Ehling (Clinic for Rehabilitation Münster, Austria) and colleagues chose 85 exercises that could be performed using minimal equipment to reduce lower limb spasticity and designed a mobile app that used videos of the exercises, along with daily reminders. They randomly assigned 94 people with moderate to severe spasticity to a 4-week inpatient program involving the exercises, along with follow up at home using the app or a paper-based program. Spasticity and mobility improved significantly with the inpatient program. At home, the improvements continued to 12 weeks with use of the app, but spasticity worsened in those using paper-based instructions. (Abstract 146
) Learn more about spasticity
Putting pressure on fatigue:
Dr. Kubra Yeni (Ondokuz Mayıs University, Samsun, Turkey) and colleagues administered acupressure, or a sham procedure, to improve fatigue in a study of 123 people with MS. They instructed participants in the acupressure group to self-administer acupressure, and then checked fatigue at two and four weeks. At two weeks, there was no significant difference, but at four weeks, fatigue was reduced in the acupressure group significantly more than in the sham group. (Abstract P915
) Find resources for acupuncture and acupressure here
MS has an “at-risk” period prior to its actual onset. Epidemiological studies have uncovered evidence suggesting that the time from exposure to risk factors and the onset of disease could be decades. ECTRIMS presenters touched on efforts to map out genetic, lifestyle, and environmental factors that contribute to the risk of developing MS. This will enable earlier intervention that may even prevent the onset of MS. Read more about what triggers MS
Timing of EBV infection:
Research findings suggest that previous infection with Epstein-Barr virus contributes to the risk of developing MS, and it precedes the onset of MS clinical signs and symptoms. Dr. Kjetil Bjornevik (Harvard T.H. Chan School of Public Health) and collaborators asked the question of whether EBV infection also occurs before possible unrecognized symptoms or hidden MS onset. If EBV is a cause of MS, EBV infection should precede the first signs of nervous system damage. The team looked for EBV antibodies in a series of stored blood (serum) samples from military personnel who later developed MS and compared them to those who did not. They found a subset whose first sample had no EBV antibodies. In this subset, they looked at concentrations of a biomarker called neurofilament light
(NfL), which indicates nerve damage has occurred. They wanted to see whether NfL levels were elevated before, around, and after the time of primary EBV infection in individuals who later developed MS. They found no signs of nerve damage before the primary EBV infection in individuals who later developed MS. In samples with EBV antibodies, NfL levels were higher in MS cases than in the controls. These findings are consistent with EBV being a trigger rather than a consequence of MS. (Abstract P378
Smoking and EBV:
Smoking has previously been identified as a risk factor for getting MS and for helping to drive progression. Dr. Lars Alfresson (Karolinska Institute, Stockholm) and collaborators explored whether a history of mononucleosis, which is an MS risk factor caused by the Epstein-Barr virus, and smoking interact to increase risk more than they each do independently. They found that current smoking, not past smoking, increased the levels of EBV antibodies in the blood and added to MS risk. (Abstract P382
COVID-19 AND MS
Naturally a big topic at ECTRIMS was COVID-19, vaccines, and the impacts of various types of disease-modifying therapies on vaccine effectiveness. MS researchers around the globe continue to collect information about how people with MS who get COVID-19 and vaccines fare, and other important questions to provide advice for people with MS. An ongoing global data sharing initiative is led by the MS International Federation to combine results from around the world to better understand and offer advice for people with MS.
Read more about MS treatments during the pandemic
Read more about COVID-19 vaccines and MS
- Dr. Anat Achiron (Tel Aviv University, Israel) reported outcomes of the Pfizer vaccine in 555 people with MS who were either on no MS therapy or were treated with strong disease-modifying therapies. They reported that the vaccine was generally safe, and that there was no increased risk of relapse after vaccination. (Abstract 003)Read more about COVID-19 and multiple sclerosis
Progress shared during the three-day meeting offers hope that finding ways to stop MS, restore function, and end the disease forever are closer than ever before.