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ACTRIMS Forum Showcases Advancements in Breaking Through Barriers to MS Cures

March 12, 2024

  • Two webinars are slated for people with MS March 13&20 
More than 1800 researchers and clinicians attended in person or online the annual Americas Committee for the Treatment and Research in MS (ACTRIMS) Forum. “Breaking Barriers” was the theme, and progress shared by presenters suggests that barriers are being turned into new opportunities to stop MS, restore function, and end MS by prevention.
  • Anyone can browse through scientific summaries (abstracts) of presentations here
  • ACTRIMS is hosting two online webinars for people with MS that will feature speakers explaining progress reported at the ACTRIMS Forum. Each will have different content. Register here to participate.
    • The first webinar will take place on Wednesday, March 13, 7:00 PM ET.
    • The second will be on Wednesday, March 20, 7:00 PM ET.
 
In most cases, results presented at medical meetings are considered preliminary until they have been published in peer-reviewed journals.
 
Stopping MS
The Pathways to Cures roadmap defines Stopping MS as achieving no new disease activity, tissue injury or worsening. Emerging research with advanced technologies is shedding light on what’s going on in the brain and spinal cord during MS and especially activities that contribute to progression. This knowledge will lead to more targeted treatments.
 
Several presentations focused on evidence that a toxic factor or factors in the spinal fluid may be causing widespread damage to tissues, and especially the outermost surface tissues of the brain.
  • For example, this presentation (by researchers at the University of Pennsylvania and collaborators) and other studies found toxic factors in the blood that are produced by immune B cells. Work is underway to further identify these factors, the chain of events that lead to their destructive activity, and ways to stop them.
 
Looking behind and ahead: Professor Anne Cross (Washington University in St. Louis) presented the Kenneth Johnson Memorial Lecture, describing some of the pivotal studies that have helped to lay the groundwork for progress in understanding and treating MS. She conducted the first phase 2 clinical trial of a B-cell depleting therapy, funded by the National MS Society, which led to the B cell therapies available today (such as ofatumumab, ocrelizumab and ublituximab). She has mentored more than 30 MS researchers making contributions to the field today and laid out several important unanswered questions whose answers will propel the field forward. (No abstract)
 
Biomarkers: Many presentations focused on refining the search for biomarkers, which are flags in the blood, spinal fluid, or imaging scans that may indicate MS disease activity, response to therapy, or may predict disease course and progression. Having validated MS biomarkers will enable precision treatments to stop MS. 
  • For example, this poster (from researchers at the Cleveland Clinic and national and international collaborators) focuses on imaging markers called the central vein sign and paramagnetic rim lesion that are being investigated as potential ways to improve the accuracy of diagnosing MS.
 
New frontiers on progression and repair: Dr. Maria Lehtinen (Boston Children’s Hospital) presented her laboratory’s research on the “choroid plexus.” This previously understudied tissue within the brain is where cerebrospinal fluid (CSF, a clear, colorless liquid that surrounds the brain and spinal cord) is produced. They have developed novel techniques for tracking choroid plexus activity in real time in mice, showing how it may lose control over inflammatory processes in MS-like conditions.
  • Lab member Dr. Alexandra Hochstetler presented further findings on autotaxin, a protein secreted by the choroid plexus. Autotaxin secretion into the CSF increases during the normal formation of nerve-insulating myelin and decreases if myelin is damaged. The team is following up on these findings to see if autotaxin represents a promising target for developing myelin-repair strategies for MS. (Poster)
 
Continuing the conference theme of breaking barriers, sessions at ACTRIMS focused on improving access to MS care and the benefits of including the voices of people with MS to improve the design and evaluation of studies and clinical trials.
  • For example, ongoing work by the European Patient Reported Outcomes initiative (PROMS) is shedding light on the need to standardize patient reported outcomes. Asking people about their hidden symptoms and quality of life issues can better inform MS care and clinical trials.
  • Barriers to MS care in the U.S.: To understand how a shortage of neurologists is affecting people’s ability to access MS care, the National MS Society commissioned a study to map out where neurologists and MS specialists practice. Society staff member Andreina Barnola presented results showing that 29% of US counties were classified as having full access to neurologists, 51% partial access, and 19% as neurology “deserts.” Looking at social drivers of health, having less access was linked to an older population, increased risk of chronic vascular conditions, depression, smoking, and less racial diversity. Efforts to improve access will need to focus on the healthcare workforce and community characteristics in targeted areas. (Poster)
 
Obesity and MS progression: Dr. Lars Alfredsson (Karolinska Institutet, Stockholm) and colleagues followed 3,249 people with MS enrolled in the Sweden MS Registry. The team assessed individuals’ Body Mass Index (a measure of body fat based on height and weight) at diagnosis and then followed them for 5 years. Those who were obese were more likely to experience MS progression faster than those who were not and were also more likely to experience cognitive issues. This study adds to increasing evidence that obesity not only affects MS risk, but also its severity. (Abstract) Get tips on controlling your weight
 
Long COVID-19 and MS: A study by Dr. Amber Salter (University of Texas Southwestern, Dallas) and collaborators focused on understanding long COVID-19 in people living with MS. Long COVID involves persistent symptoms and has been found to occur in 23% of people studied in the general population. A survey of people with MS enrolled in the NARCOMS registry found that following COVID infection much fewer people with MS reported new symptoms that meet the definition of long COVID compared to the general population. However, when looking at new and pre-existing MS symptoms like fatigue, brain fog and vision issues, the frequency of those living with MS who report symptoms that meet the definition of long COVID is similar to the general population. This makes it difficult to evaluate long COVID in people with MS. This study was supported by a Strategic Initiative award from the National MS Society. (Abstract)
 
Ocrevus study includes Kenya:  Dr. Jugena Smith (Genentech, Inc., South San Francisco) and colleagues previously reported initial results from the CHIMES trial, an open, unblinded trial of ocrelizumab involving 113 Black and 69 Hispanic/Latinx people with relapsing MS. Now the team presented data from 10 people who enrolled at the study site in Kenya, Africa. After one year of this ongoing study, 6 people had no evidence of disease activity, 8 had experienced no relapses, no one experienced disease progression, and most were free of disease activity on MRI scans. The side effects that occurred were similar to those in the pivotal ocrelizumab trials. Further results of this trial will help in understanding MS treatment responses in underserved populations. (Abstract)
Learn more about MS in the Black and Hispanic/Latinx communities
 
Disappointing trial results: Dr. Xavier Montalban (Cemcat, Barcelona) presented the first details of two large phase 3 trials of evobrutinib that failed to prove this “BTK inhibitor” was superior to teriflunomide. This compound, and others like it that are still under study, are thought to suppress immune B cells and also may inhibit immune cells called microglia that reside in the brain and are thought to contribute to disease progression. Both therapies reduced annual relapse rates, which was the primary end point of the study, but evobrutinib was not shown to do a better job of this or other outcomes measured. (Abstract)
 
Restoring Function
The theme of breaking through barriers continued in the area of restoring function. This included a session on barriers to repairing the damage to nerve-insulating myelin and detecting repair in clinical trials. An ongoing issue is how to quickly detect whether repair has been successful. Several presentations showed progress toward this goal using advanced MRI, optical coherence tomography (OCT) and positron emission tomography (PET).
 
Barriers in rehabilitation include the need for more research on the types and “doses” of exercise and rehabilitation to maximize function and rebuild brain connections, and the need for more evidence of the benefit to increase people’s access to rehabilitation. A panel of experts discussed how to ensure that rehabilitation research can fulfill its potential for restoring function widely in people with MS.
  • Dr. Don Mahad (University of Edinburgh) noted that the nature of MS holds promise for the success of rehabilitation therapies. Unlike other nervous system diseases or injuries, nerve cell bodies remain mostly intact in MS. Also, there is a period of malfunction before serious injury, where rehab interventions may delay or even prevent nerve degeneration.
  • Dr. Rob Motl (University of Illinois, Chicago) advised on how to improve exercise study results, urging researchers to conduct discovery trials testing, for example, a single session of exercise. The results can help to determine the most effective parameters for a full study.
Learn how everyone with MS benefits from rehabilitation
 
Other presentations included:
Gut microbiome and myelin repair: National MS Society Postdoctoral Fellow Dr. Larissa Jank (Johns Hopkins University) presented her team’s work related to a molecule called Indole 3-lactate (ILA), a breakdown product of the dietary amino acid tryptophan whose levels are controlled by gut bacteria. ILA blood levels have been found to be reduced in MS, especially progressive MS. In lab mice, feeding them ILA promoted myelin repair after injury and dampened inflammation. ILA is found in fermented foods, but more work is needed to see whether increasing the intake of ILA or tryptophan will be restorative in people with MS. (Abstract)
 
Breaking immune barriers to myelin repair: Immune cells that reside in the brain called microglia provide benefits and barriers to the repair of nerve-insulating myelin, depending on their environment. Dr. Jeffrey Huang (Georgetown University) described a series of studies to figure out what might be impeding repair in MS lesions. His team tested a compound that drove the repair-promoting activities of microglia in mice. The compound enhanced the survival of myelin-making cells, and other studies suggested it could reduce inflammation. This approach is undergoing further early testing by J-Pharma, with support from the Society’s Fast Forward commercial research program, to explore its potential as a future repair strategy in MS. (No abstract; Related Poster)
 
More results on mesenchymal stem cells: Research to understand the potential of individuals’ own mesenchymal stem cells (MSC - adult stem cells found in bone marrow, skin, fat and other tissues) to stop inflammation and promote myelin repair in MS has been ongoing. Drs. Petrou Panayiota, Dimitrios Karussis and team (Hadassah University Hospital, Jerusalem) are conducting an extension to a previously reported trial of up to three treatments of MSCs infused into the spinal fluid of people with active progressive MS. The original trial suggested benefits. Reporting from this ongoing extension study related to the first 23 participants, they found significant improvements in walking ability, cognition, self-reported quality of life, along with reductions in blood biomarkers (sNfL and GFAP) that reflect brain tissue damage. No serious adverse events have occurred. This study is ongoing. (Abstract
Learn more about MS and stem cells 
 
New tool for identifying myelin repair compounds: Dr. Krystyn Van Vliet (Cornell University) described a new tool her team has developed to advance the study of myelin repair. The tool consists of microscopic artificial axons (nerve fibers) that have the stiffness of real axons. They add myelin-making cells from rats and screen compounds to find ones that promote myelin wrapping around the axons. Now they plan tests in human cells and introduce inflammatory factors to better reflect the MS lesion environment. (No abstract; Recent paper in Scientific Reports)
 
Ending MS
Ending MS will mean no one will ever again hear the words, “You have MS.” One strategy to prevent MS is to identify and limit exposure to MS risk factors. Several ACTRIMS presentations and posters focused on understanding how Epstein-Barr virus (EBV) is involved in launching and possibly sustaining MS disease activity. There is no answer yet, but research is ongoing. Other studies of note included:
 
Big Data to End MS: Dr. Sergio Baranzini (University of California, San Francisco) received the Barancik Prize for Innovation in MS Research and presented the prize lecture. He emphasized the power of large collaborations and big science to solve the complex questions around MS. These include his leadership in the International MS Microbiome Study and the International MS Genetics Consortium. About winning the Prize, Dr. Baranzini noted, “I hope this inspires a fresh wave of collaborative researchers in the MS field to take on the remaining crucial challenges in our quest to stop, restore, and end MS.” (Read more)
 
Global MS research investment: The newly formed Global MS Research Strategy Group, representing major MS research organizations around the world, commissioned a study to better understand the landscape of MS research by non-profit and government organizations worldwide. Top-line results showed that at least 1,305 research projects have been funded by 16 non-profits including the National MS Society during 2021-2023. These were valued at over €379 million ($390 million) and represent all three Pathways to Cures categories. Over 950 government research projects, valued at 1 billion Euros, were identified. Further analysis is ongoing to identify gaps and opportunities for multidisciplinary collaborations. MS organizations have jointly declared their collective commitment to a global research strategy to accelerate cures for MS. Global cooperation and alignment of resources will accelerate progress towards knowledge, treatments, and cures for MS. (Abstract) (Poster)
 

These and many other presentations at the ACTRIMS Forum 2024 make it clear that researchers around the world are making critical advances toward the day when there are solutions for everyone living with MS.
 
 

About Multiple Sclerosis

Multiple sclerosis is an unpredictable disease of the central nervous system. Currently there is no cure. Symptoms vary from person to person and may include disabling fatigue, mobility challenges, cognitive changes, and vision issues. An estimated 1 million people live with MS in the United States. Early diagnosis and treatment are critical to minimize disability. Significant progress is being made to achieve a world free of MS.

About the National Multiple Sclerosis Society

The National MS Society, founded in 1946, is the global leader of a growing movement dedicated to creating a world free of MS. The Society funds cutting-edge research for a cure, drives change through advocacy and provides programs and services to help people affected by MS live their best lives. Connect to learn more and get involved: nationalMSsociety.org, Facebook, X, formerly known as Twitter, Instagram, YouTube or 1-800-344-4867.

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