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Emerging MS Therapies, Advances in Brain Science Among Themes of AAN Meeting

May 11, 2018

More than 10,000 neurologists and researchers from around the world gathered for the American Academy of Neurology’s annual meeting held in Los Angeles in April. Sessions focused on many MS topics including emerging therapies, imaging and other ways to track MS activity, and addressing cognitive function.  Advances were reported from many different avenues of research, driving breakthroughs that will stop MS, restore function and end MS forever. Below are a few highlights. Studies presented are considered preliminary until they are published in peer-reviewed journals.
Stopping MS: Emerging Therapies
Many studies presented at the AAN showed continued benefits of available therapies and longer-term safety information, as well as more evidence that early and ongoing treatment with a disease-modifying therapy has long-term benefits for controlling disease activity, delaying accumulation of disability and protecting quality of life.
Early vs Later Treatment – Using data that captures information from virtually everyone in Denmark living with MS, PhD student Thor Chalmer and colleagues (University of Copenhagen) reported that individuals who began disease-modifying therapy within two years of their first symptom progressed more slowly compared to those who started therapy later. This study was funded by the Danish MS Society and others. Read the abstract
Laquinimod for primary progressive MS –  First details were presented from the international phase 2 clinical trial of oral laquinimod in primary progressive MS. The trial involved 374 people randomly assigned to a lower or higher dose of the treatment or placebo. After two years, no significant difference was seen in changes in brain volume or progression of disability between those on laquinimod and those on placebo. Although the trial was negative, the results offer important clues to designing future clinical trials in progressive MS. Read the abstract
HSCT/bone marrow stem cell transplants -- Dr. Richard Burt (Northwestern University) reported interim results of an international clinical trial of HSCT (autologous hematopoietic stem cell transplant – read more) involving 110 people with active MS whose disease had not responded to disease-modifying medications. Half stayed on their medication and half underwent HSCT. So far, the team reports that one year after enrollment, no severe toxicities or deaths have occurred in those who received the transplants. One MS relapse occurred in the transplant group versus 39 relapses in those continuing their medication. The team also reported improvement in MS disability in those who had received the transplants. Further details will be available when the 5-year study is completed and results published. Additional controlled trials, now underway or in planning stages, will help determine who may respond best and which approach to HSCT is optimal for treating MS. Read the abstract; read more about HSCT
MRI findings from trial of fingolimod in kids with MS – An international team presented additional data from the largest clinical trial yet in children and teens with MS, which found that fingolimod (Gilenya®, Novartis) significantly reduced relapses after two years compared to interferon beta-1a (Avonex®). Imaging results suggested that fingolimod reduced the risk of developing new or newly enlarging MRI lesions as well as inflammatory (gadolinium-enhancing) lesions. Fingolimod also slowed the loss of brain volume. Novartis has applied to the FDA to expand the use of fingolimod to include pediatric MS. Read the abstract
Treating pediatric MS -- Children who develop MS are being prescribed disease-modifying therapies approved for adults. National MS Society Sylvia Lawry Fellow Dr. Kristen Krysko (University of California, San Francisco) and team wanted to see which therapies were being prescribed and detect any safety issues. Using data collected by the 12 Society-supported U.S. Network of Pediatric MS Centers from over 1,000 children, they found that 78% had received at least one disease-modifying therapy, and that there’s been an increase in the use of newer therapies such as oral and infused therapies over time. No new side effects had been reported beyond what has been reported in adults. The team noted the need for research on the long-term effectiveness and safety of these therapies in children. Read the abstract
New Treatment Guidelines – During the meeting, the AAN released a Practice Guideline to help healthcare professionals and people with MS choose among available disease-modifying therapies. It summarizes different types of therapies and evidence about their effectiveness in reducing relapses and slowing progression, potential risks and side effects, and when to consider switching from one therapy to another. The guideline was developed by a panel of experts, including people living with MS. Read more
Stopping MS: Tracking Disease Activity and Progression
More Evidence of Faster Disease Progression -- A team led by Dr. Peter Calabresi (Johns Hopkins University) reported additional evidence that African Americans experience faster MS progression and nervous tissue loss. The team used brain MRIs and optical coherence tomography to track structural changes at the back of the eye, comparing African Americans with MS with Caucasians with MS. Their results showed that nerve tissue loss occurred faster in African Americans, suggesting that this population may benefit from more aggressive treatment.  Read the abstract
Blood marker indicates slowing of damage? Being able to quickly measure the response to an experimental treatment using a biomarker would accelerate the development of new therapies for MS. Several presentations focused on the presence of fragments of nerve fibers called neurofilament light chains (NfL) in the spinal fluid or in the blood. In one, an international team looked at NfL in blood samples from people who had participated in three large-scale MS clinical trials. They found that higher levels were linked to higher disease activity, and lower levels to less or stable disease activity. In addition blood NfL levels went down in the drug treated arms. Further verification of NfL as a biomarker of treatment response could improve clinical trials and ultimately clinical care. Read the abstract
Dystel Prize for Leader in MRI -- Frederik Barkhof, MD, PhD (VU University Medical Center in Amsterdam and University College London), was chosen by a committee of his peers to receive the National MS Society/AAN’s 2018 John Dystel Prize for Multiple Sclerosis Research. He was honored as a leader in using MRI to improve the diagnosis of MS, to better understand the disease, and to speed the search for better therapies. Read more about his contributions and the Dystel Prize.
Restoring Function
Impacts on Cognition – Several studies focused on whether the latest approved or still experimental disease-modifying therapies have any benefits for cognitive problems associated with MS. International teams of researchers who conducted clinical trials of ocrelizumab in relapsing MS and siponimod in secondary progressive MS evaluated data from those trials. Both reported improvements and/or lower risk of worsening cognitive scores in those treated with these therapies. Read the abstract on ocrelizumab; read the abstract on siponimod
New insights into brain networks -- Dr. Jeff Lichtman of Harvard University gave a talk about his team’s work using advanced computing and microscopy to piece together and color code virtually every component of the brain. The results provide what he calls “digital tissue” and it’s especially useful for teasing out how brain cells connect and interact. This intricate work could lead to new insights for correcting neurological conditions like multiple sclerosis. Watch a talk by him on YouTube
Telemedicine to improve care –  Dr. Riley Bove (University of California, San Francisco) and team studied doctor and patient satisfaction with the use of televideo clinical checkups for people with MS as a way of reducing the burden of traveling to appointments. The participants had video visits (“telemedicine”) as well as in-person clinic visits as part of their regular care. Overall, both the doctors and their patients reported satisfaction with this approach. Many were saved from many miles of travel, hotel stays and missed days of work. Read the abstract

Ending MS
Progress has been made in identifying key biological pathways that contribute to MS risk, but the cause is still unknown. Both genetic and environmental risk factors have been implicated for increasing the risk of developing MS. (Many people have MS risk factors and will never develop MS, and many people develop MS without having been exposed to identified risk factors.)  Read more about risk factors and MS
Does eating fish reduce risk of MS? Dr. Annette Langer-Gould (Kaiser Permanente Southern California) and team examined the diets of 1,153 people from a variety of backgrounds, about half of whom had MS or clinically isolated syndrome (CIS - an initial neurological attack that may or may not become MS). The team reported a reduced risk of MS/CIS among those whose intake of fish was considered high – defined as either eating one serving of fish per week or eating one to three servings per month plus taking daily fish oil supplements. They also identified two gene variants related to fatty acid metabolism that linked to lower risks of MS, independent of fish intake. While the study adds to previous research suggesting that eating fish or omega-3 fatty acids may play an important role in reducing MS risk, the authors emphasize that an identified link such as this one does not prove cause and effect. Read the abstract

When do risk factors influence MS? Dr. Dalia Rotstein (University of Toronto) and colleagues investigated factors that may play into MS susceptibility by studying the health experience of immigrants to Ontario, which has a high prevalence of MS. Historic studies suggest that there may be a window of risk exposure that helps dictate whether a person will develop MS, and immigrants of different ages either retain the risk rates of their country of origin or take on the risk rates of their new home, depending on that window. The researchers found that in general, immigrants developed MS less often than natives of Ontario, and that the older they were on arrival, the lower their risk of developing MS. However, immigrants from the Middle East had higher rates of developing MS, and the longer the interval since arrival, the greater the risk of developing MS. The team suggested that war zone environmental factors may play a role in the increased risk of MS in those from the Middle East. Read the abstract
Puberty and risk of MS – An international team presented results of study that looked at the potential influence of age at puberty with the risk of developing MS. They used genetic data gathered by the International MS Genetics Consortium and others and examined gene variants that control age at puberty. They found that the lower the age of puberty, the higher the risk for developing MS. Further study determined that this effect was largely due to the influence of obesity, and if obesity was not an added factor, they found that age at puberty was no longer a strong MS risk factor. Read the abstract 
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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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