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Emerging MS Therapies, Advances in Stopping Progression and Restoring Function Among Themes of AAN Meeting

May 17, 2019

More than 10,000 neurologists and researchers from around the world gathered for the American Academy of Neurology’s annual meeting held in Philadelphia in May. Sessions focused on many MS topics including emerging therapies, imaging and other ways to track MS activity, progressive MS, and reversing symptoms.   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/stopping progression
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.
 
A different way to target B cells: New results were reported by Dr. Xavier Montalban (University of Toronto, Ontario) from a phase 2 trial of evobrutinib – an oral therapy that targets B cells, but with a different mechanism of action than Ocrevus. Evobrutinib inhibits an enzyme called “Bruton’s tyrosine kinase,” reducing the activation of B cells and inhibiting immune cells called microglia, which have been linked to MS progression. At 24 weeks, the team previously reported that the experimental therapy was fairly well tolerated and reduced the occurrence of active MRI brain lesions in people with relapsing MS. At the AAN, Dr. Montalban reported that these results were maintained through 48 weeks. (Abstract S56.004)
 
Can addressing vascular risk factors slow MS? Dr. Vijayshree Yadav (Oregon Health & Sciences University) described a study of people with MS with “vascular risk factors,” such as high blood pressure, diabetes, heart disease, obesity and high cholesterol. The team compared people with and without vascular risk factors. Over three years, they found that those with these conditions had more fatigue, higher disability scores, lower brain volume and reduced brain ATP (which carries energy inside cells). Further study is necessary to determine whether treating vascular conditions may improve MS symptoms and progression. (Abstract S55.001)
 
Reducing the risk of PML: Researchers at New York University and others added evidence suggesting that giving Tysabri infusions every 6 weeks, instead of the standard dose of every 4 weeks, may reduce the risk of PML (progressive multifocal leukoencephalopathy) in individuals who test positive for the JC virus. PML is a known, serious or fatal brain disease that has occurred in individuals taking Tysabri and some other powerful disease-modifying therapies. A study is ongoing to confirm these findings in 480 people with MS. These data can better define risks and inform treatment decisions. (Abstract S26.006)
 
Dystel Prize for pioneering neurologist: Anne H. Cross, MD (Washington University, St. Louis) was chosen by a committee of her peers to receive the National MS Society/AAN’s 2019 John Dystel Prize for MS Research. She is being honored for wide-ranging translational research including early work on the key role of B lymphocytes (immune cells) in driving MS immune attacks, and investigation of new imaging techniques to detect disease activity. Read more about her contributions and the Dystel Prize.
 
Challenging views on pregnancy in MS: Several teams reported findings that indicate that pregnancy may be safer than previously considered for women with MS, and that more education is needed for both healthcare providers and women considering pregnancy:
  • Dr. Annette Langer-Gould (Kaiser Permanente Southern California) and her team looked at outcomes of 466 pregnancies among 375 women with MS. The group as a whole had milder disease and fewer than expected relapses after pregnancy. The team also reported that exclusive breastfeeding further reduced the risk of postpartum relapses. (Abstract S6.007)
  • Dr. Maria Claudia Manieri (Brigham and Women’s Hospital) reported on PREG-MS, an ongoing study following women with MS at 11 MS centers in New England for up to three years postpartum. Reporting on 143 cases, they noted that 51 were mistakenly designated as “high risk” pregnancies by healthcare providers, since the women did not experience unusual pregnancy complications, adverse outcomes, or the risk for a relapse during or after pregnancy. (Abstract S27.006
The shift from relapsing to secondary progressive: Dr. Antje Bischof (University of California, San Francisco) presented a novel approach to study spinal cord shrinkage over time in people with MS, who had multiple brain MRI scans over 12 years, but not spinal cord scans. The team was able to track the size of the very top of the spinal cord, where it meets the base of the brain. They compared people who transitioned to secondary progressive MS to those who did not. In those who transitioned, they found early signs of more rapid spinal cord atrophy, or shrinkage, at least 4 years before the transition. If confirmed, having this kind of predictive biomarker would improve clinical trials and treatment decisions. (Abstract S12.001)
 
Progression from the individual’s viewpoint: Dr. Ilya Kister (New York University) and colleagues developed “SymptoMScreen” as a clinical tool that captures how progression impacts people with MS, by assessing severity of 12 common MS symptom areas: walking, dexterity, spasticity, bodily pain, sensory, bladder, fatigue, vision, dizziness, cognitive, depression, and anxiety. Testing nearly 600 people, they found that the main drivers of increases in symptoms were in the areas of bladder, dexterity and dizziness, and that worsening symptoms predicted worse disability scores. (Abstract S26.009)
 
Restoring Function
The hopes of people living with MS today rest on finding a way reversing damage to the nervous system to protect the brain and restore lost function. Restoring function also means finding ways to understand and address unpredictable symptoms to improve quality of life.
 
Myelin repair trial completed: Dr. Scott Newsome (Johns Hopkins University) reported results from a small, open label trial of a thyroid hormone mimic called liothyronine, funded by the National MS Society. Treatment was generally well tolerated, with GI symptoms being the main side effect. This kind of small study isn’t designed to detect actual repair of nerve-insulating myelin, but the team is now analyzing other outcomes to determine whether a phase 2 trial is warranted. (Abstract S56.003)
 
New clinical trials for myelin/nerve repair: Two new phase 2 trials were reported to be underway to test the experimental treatment elezanumab, one in people with progressive MS, and one in people with relapsing MS. In lab models elezanumab was able to promote repair of axons and myelin and protect against damage. Results of a phase 1 trial showing safety were originally reported last fall at ECTRIMS. Elezanumab inhibits a molecule that plays a role in stopping the outgrowth of nerve endings during development. (Abstract S56.001)
 
Rewiring the brain: Dr. Giacomo Boffa (University of Genoa) and colleagues tested whether exercises for the hands and arms could improve function more than passive movements in 35 people with primary or secondary progressive MS. Motor performance improved, and fatigue was reduced in the active treatment group. There also were improvements in “functional connectivity,” or communication lines between specific brain regions. This adds to evidence that the brain has the power to compensate for MS damage. (Abstract S33.002)
 
Early study of antioxidant for fatigue: Dr. Krysten Krysko (University of California, San Francisco) presented the findings of a novel, small clinical trial in 15 people with progressive MS who had fatigue. Her team showed that the antioxidant N-acetyl cysteine was well tolerated, reduced fatigue, and affected biological indicators of oxidative damage. Larger trials may be warranted to see if this antioxidant can reduce fatigue and possibly protect the nervous system from damage in progressive MS. (Poster P5.2-093)
 
What does electrical stimulation do to the brain? Claire Choi, a research analyst working with Dr. Leigh Charvet (New York University) reported on an effort to find out why transcranial direct current stimulation (tDCS, which involves low electrical current delivered via electrodes) seems to improve some MS symptoms. The team found hints that tDCS increased some metabolic processes and nerve cell reactivity in the brain of people with MS, and they plan to confirm these findings in larger numbers of people. (Abstract S33.004)
 
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. Read more about risk factors and MS
 
MS onset – early and late: Farren Briggs, PhD (Case Western University) pinpointed several genes associated with earlier onset of MS. His team screened more than 1,000 people with MS for 200 genes to determine associated with age of onset. (Abstract S49.001) Meanwhile, Smathorn Thakolwiboon, MD (Texas Tech University) and colleagues found that 15% of a group of 314 people were diagnosed with MS after age 50; this is a higher percentage of “late onset” MS than previously observed. (Poster P4.2-075)
 
Gut bacteria and MS risk in adults: A team led by Dr. Phil De Jager (Columbia University) looked at links between diet, gut bacteria (microbiome) and other factors in 93 people who have no symptoms but who have close family members with MS, and thus are at potentially higher risk for developing MS. This team previously developed a “risk score” by weighing a person’s known risk factors (such as MS-related risk genes and environmental exposures like smoking). Participants gave stool samples and completed surveys about their diets. Among their findings, those with the highest risk scores tended to have fewer gut bacteria that produce short-chain fatty acids, which have been linked to calmer immune systems and may be protective against immune-mediated diseases. This is just one example of an unfolding story that may lead to approaches for stopping or preventing MS. Dr. De Jager received the prestigious Harry Weaver Neuroscience Scholar Award from the Society and the 2014 Barancik Prize for Innovation in MS Research. (Abstract P4.2-056)

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. 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. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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