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Biomarkers, Diet, Progressive MS, and Epstein-Barr virus Among Research News Shared at ECTRIMS

November 4, 2022

Advances were reported from many different avenues of research at the 2022 ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) conference in Amsterdam. This year the world’s largest MS research conference was attended in person or virtually by over 8,700 people from more than 100 countries.

Below are only a few highlights of many important presentations, grouped according to three Pathways to Cures that will stop MS, restore function, and end MS by preventing new cases.
   
Usually, study results presented during conferences like this are considered preliminary until they are published in peer-reviewed journals.

STOPPING MS

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.
 
BTK inhibitors: The conference was an indicator of growing attention to immune cells in the brain called microglia, which have been linked to MS progression and can play both beneficial and harmful roles in MS. Several studies explored these roles with the goal of finding ways to eliminate the bad players and enhance the good. One up and coming experimental approach is “BTK inhibition.” Results from phase 3 clinical trials in both progressive and relapsing MS are expected to be released at future conferences. BTK inhibitors are thought to both inhibit microglia and to reduce the activation of immune B cells involved in MS.
 
Tracking MS: Many studies presented at ECTRIMS reported on efforts to determine how to predict an individual’s disease course and progression to guide better treatment decisions. There has been steady momentum in the development and standardization of biomarkers in the blood and spinal fluid to aid this process, which would also speed clinical trials in progressive MS. Imaging tools, such as MRI and PET, are also being refined. Large-scale international collaborations are helping to propel this work.
 
Some specific studies reporting advances in the Stop Pathway include:
Vitamin D fails to reduce MS activity: Low levels of vitamin D in the blood have been reported by many groups to be a risk factor for MS. This knowledge inspired two large trials testing the idea that supplementation with Vitamin D could reduce ongoing MS disease activity. Both studies reported that high doses of vitamin D did not reduce MS disease activity (clinical or imaging). These studies don’t tell us whether people with severe vitamin D deficiency would receive benefit from vitamin D supplements, or whether vitamin D can prevent MS from developing before any symptoms occur.
  • U.S. Study: A National MS Society-funded clinical trial conducted by Dr. Ellen Mowry of Johns Hopkins University and colleagues compared high doses (5000 International Units per day) versus low doses (600 International Units per day) of vitamin D supplements in people with relapsing-remitting MS who were taking daily injections of Copaxone. After 96 weeks, among 140 people who completed the trial, the was no evidence that high-dose vitamin D supplements reduced MS activity, including relapses and MRI-detected brain lesions. (Abstract P301)
  • Australia-New Zealand Study: A trial conducted by Dr. Helmut Butzkueven and others tested multiple dose levels (1,000, 5,000, or 10,000 IU per day) compared to inactive placebo in 204 people with clinically isolated syndrome (CIS) and who were not being treated by an MS disease-modifying therapy. (People with CIS have experienced a first episode of a neurological symptom that may or may not develop into definite MS.) After 48 weeks, the investigators found no difference in the number of people in each treatment arm who went on to develop definite MS. This trial was funded by MS Australia, with additional support from the National MS Society. (Abstract P1206)
Read more about these studies   Learn more about vitamin D and MS
 
Understanding pediatric MS: Dr. Brenda Banwell (University of Pennsylvania) gave the ECTRIMS Lecture focusing on how far we’ve come in the understanding of MS that begins in childhood, and how its study also brings insight into mechanisms in adult-onset MS. It can impact brain growth and cognition. She noted that pediatric MS is always relapsing-remitting MS, and disease-modifying therapy has proven helpful, along with wellness strategies such as physical activity and proper diet. “Wellness is therapy,” she emphasized. The National MS Society has provided ongoing support for the U.S. Network of Pediatric MS Centers to foster research and improve care for this vulnerable population.
 
Genes related to disease progression: Over 230 gene variations have been uncovered by members of the International Multiple Sclerosis Genetics Consortium. These variations contribute to people’s risk of developing MS, but the role of genes in the disease course remains unclear. Dr. Adil Harroud (McGill University, Montreal) presented results on behalf of the consortium suggesting that two gene variations contribute to MS severity, increasing the speed of disability progression. The variations are near genes expressed in the brain that could regulate resiliency to damage caused by MS and may offer new therapeutic targets. Dr. Harroud is funded by the National MS Society and the MS Society of Canada. (Abstract 0068
 
Intermittent fasting: With funding from the National MS Society, Dr. Laura Piccio (Washington University in St. Louis) and colleagues conducted a small clinical trial comparing intermittent fasting with typical western diet over 12 weeks in 42 people with relapsing MS. From a previous study they found that intermittent fasting (eating about 500 calories/day for two days/week) modulated the blood levels of “leptin” and “adiponectin,” molecules that relate to inflammation. In this study, intermittent fasting increased levels of adiponectin, reduced MRI-detected inflammation, and appeared to produce potentially beneficial changes in brain structures. Additional analyses are ongoing. (Abstract P169) Learn more about diet and MS
 
Fertility treatments and MS: Dr. Edith Graham (Northwestern University, Chicago) and collaborators wanted to know whether the hormone fluctuations caused by fertility treatments such as in vitro fertilization could increase the risk of MS relapses. The team tracked 110 cycles of fertility treatments in 55 people with MS or Clinically Isolated Syndrome. They reported finding no significant elevated risk of relapses after fertility treatments, and relapse rates dropped with successful pregnancies. (Abstract O040) Read more about pregnancy and reproductive issues

RESTORING FUNCTION

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. An emerging theme at ECTRIMS was brain connections – the complex circuitry that can be disrupted by MS and how maximizing myelin repair and cognitive rehabilitation strategies could preserve and/or repair these circuits. Scientists described the importance of identifying brain networks to evaluate how they underly development across the life span and may lead to predictive models of cognitive decline in MS.
 
The Rehabilitation in MS (RIMS) organization joined ECTRIMS at this year’s meeting, providing a more expansive view of rehabilitation science and wellness. Sessions focused on the impact of age on physical function, the use of technology to support rehabilitation and creative new strategies in vocational rehabilitation and symptom management to maximize abilities and treat troubling symptoms. Some specific studies illustrating advances in the Repair Pathway include:
 
Bile acid supplements: People with MS may have abnormalities in the way they process energy and other maintenance activities. Bile acids are produced by the liver and help the body absorb fats (lipids) in the gut and can influence the composition of gut bacteria and interact with immune cells and brain cells. A National MS Society-funded clinical trial conducted by a team led by Dr. Pavan Bhargava (Johns Hopkins University, Baltimore) compared supplemental bile acids (tauroursodeoxycholic acid) to placebo for 16 weeks in 59 people with progressive MS. The team is still evaluating results on gut bacteria, but they reported that the supplement was safe and showed some improvement in the MS Functional Composite, a measure of physical and cognitive performance. (Abstract P1191)
 
Work is good for health: So noted Blanca De Dios Pérez (University of Nottingham), adding, “And vocational rehabilitation is the process whereby those affected by illness or disability are able to remain at work.” Her team conducted 20 interviews with people with MS, employers, and healthcare professionals. These showed that cognition, fatigue, and mobility were the most common symptoms causing problems at work, and that negative attitudes of employers and coworkers played a role as well. Using this information, the team developed a job retention approach that targeted both employees and employers. In a small study, the approach was feasible and acceptable and improved attainment of work-related goals for the employees. (Abstract O149) Can vocational rehabilitation work for you? 
 
Online treatment for depression: Dr. Stefan Gold (Charite Universitätsmedizin Berlin, Germany) and international colleagues tested a 12-week computerized cognitive behavioral program – called deprexis® (Orexo AB) – for overcoming MS-related depression in 279 people with all forms of MS. This study was funded by the National MS Society, and the company provided free access to participants. The program was reported to be safe, reduced depression, improved quality of life, but did not affect fatigue. Benefits were maintained up to 12 months. Dr. Gold emphasized that this program does not completely cure depression but is an option to consider even early in depression treatment or if in-person care is not available. Research like this to validate a program’s benefits is an important step toward getting coverage by health insurers. (Abstract O115) Read more about getting help for depression

ENDING MS

Preventing MS will require a better understanding of how risk factors lead to the development of the disease so that exposures to these factors can be limited. Many gene variations have been identified that contribute to a person’s susceptibility to MS, but even in identical twins with identical genes, having MS genes is not sufficient to cause the disease.
 
There is growing attention to the question of when MS actually begins, and whether recognizing it early, or even before onset, can stop or even prevent the disease. At ECTRIMS there were many studies related to Epstein-Barr virus (EBV) and how it acts as a trigger for MS. Several studies confirmed recent findings and explored potential mechanisms for how this virus that infects nearly everyone could trigger MS when coupled with other MS risk factors. Here are a few specific studies showing advances in the End pathway:
 
Timing of EBV infection: Dr. Daniel Jons (University of Gothenburg, Sweden) and colleagues examined blood that had been banked from 669 people who eventually developed MS, compared to people who did not develop MS. They looked for antibodies against EBV and the presence of a biomarker of nerve damage called neurofilament light chain (sNfL). All MS samples showed signs of EBV exposure 15 to 20 years before an MS diagnosis. NfL levels began to rise later, from 5 to 10 years before MS onset. This suggests that EBV exposure occurred before nerve damage began. (Abstract 0111)
 
Can MS be delayed or prevented? Dr. Darin Okuda (UT Southwestern) and an international consortium treated 87 people with oral Tecfidera or placebo over 96 weeks. The participants all had the rare phenomenon called Radiologically Isolated Syndrome (RIS). In RIS, there are MS-like brain lesions on MRI but no detectable symptoms. Previous research suggests that about half of those with RIS are likely to develop definite MS within ten years. The results of this trial suggest that treatment significantly reduced the risk of having a first neurological symptom, compared to those on placebo. No unexpected side effects emerged. This first completed trial of its kind adds to the idea that early treatment is protective and supports the idea that MS can begin well before symptoms emerge. (Abstract 0179)
 
B cell activity in spinal fluid: A big question in the MS field is why most people with MS have antibodies in their spinal fluid (called oligoclonal bands) and persistent production of other antibodies, and what is stimulating the production of those antibodies by immune B cells. Drs. Ilaria Callegari, Tobias Derfuss (University of Basel) and collaborators used advanced tools to analyze spinal fluid samples from hundreds of people with MS and people without MS. They identified a specific antibody from MS samples that bound to nerve cells and microglia in samples of human MS lesions. Their work to determine the exact target of the antibody continues. This approach has the potential to identify a trigger of MS immune activity, which might be targeted with a therapy to stop it. (Abstract 0044)

COVID-19 and MS

COVID-19, vaccination, and timing of MS treatments continue to be important research topics for the MS community and the focus of several presentations at ECTRIMS. One unique study reported by Dr. Maria Grazia Aprea (University of Florence, Italy) tracked health outcomes of COVID-19 infection contracted during pregnancy, which included 85 women in Italy and Turkey. Their results suggested that pregnancy did not increase the risk for severe infection. They are still following many of these women but among a small group who have already given birth, they did not see differences in maternal or fetal health compared to a pre-pandemic group of pregnant women with MS. (Abstract 0140)
Read the latest guidance about MS and COVID-19

This and other progress shared during the ECTRIMS meeting offers hope that finding ways to stop MS, restore function, and end the disease forever are closer than ever before. Read more about Pathways to MS Cures
 

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.

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