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Progressive MS, Emerging Therapies, and New Clues to Restoring Function Among Topics at AAN Meeting

May 10, 2017

About 14,000 neurologists and researchers from around the world gathered for the American Academy of Neurology’s (AAN) annual meeting held in Boston in April. Sessions focused on many topics including emerging therapies, imaging and other ways to track MS activity, progressive MS, and approaches to restoring function.   
 
Read Blogs from the AAN: Browse abstracts (scientific summaries) or follow links below to specific study abstracts. 


Stopping MS

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.
 
Dystel Prize Winner Champions Research on Progressive MS: The John Dystel Prize for MS Research was awarded to Professor Alan Thompson of University College London. Dr. Thompson has made significant contributions to the understanding of progressive MS, including in his role as the chief scientific advisor for the International Progressive MS Alliance. Read more about his important contributions and the Dystel Prize. The Prize was awarded during a scientific session focused entirely on progressive MS, a first for the AAN meeting. “There’s been progress, but still an awful lot more to do,” Prof. Thompson noted during his invited talk.
 
Targeting EBV to Treat Progressive MS: Australian researchers are taking a new approach to treat progressive MS. Infection with the Epstein-Barr virus (which can cause mononucleosis) has long been suspected as a possible trigger for MS. Drs. Michael Pender, Rajiv Khanna (University of Queensland and Royal Brisbane and Women’s Hospital) and others speculated that EBV infected B-cells (white blood cells that help fight infections) might have a role. The team presented initial results from a small, open-label clinical trial that targeted these cells for destruction by amplifying the body’s natural immune response against virus-infected cells. The results suggest they might be on the right track, but the study needs to be completed and analyzed before it is known whether this approach is safe and worth pursuing. (Late-Breaking Abstract)
 
Protecting the Brain from Harm: With National MS Society funding, Drs. Matthew Bellizzi, Harris Gelbard and team (University of Rochester) have been trying to prevent MS damage that occurs to synapses (the interfaces between nerve endings that relay messages throughout the nervous system). They reported on tests of a compound called URMC-099, which targets microglia, immune cells in the brain that contribute to ongoing destruction to nerves in the course of progressive MS. In mice with the MS-like disease EAE, they found that giving this compound de-activated microglia and protected synapses and nerve cell function in a part of the brain that is hard hit in MS – the hippocampus. More research is needed before this approach to stopping damage and progression can be tested in people. (Abstract P1.396)
 
When to Stop Therapy: In an invited debate, Drs. John Corboy (University of Colorado) and Rob Naismith (Washington University, St. Louis) discussed whether and when in later stages of a person’s experience with MS should they stop taking disease-modifying therapies. It was noted that there is no way to predict whether a person’s MS relapses have diminished because their therapy is working well or because their MS disease activity has abated with age. Dr. Naismith argued against discontinuing treatment because people can have ongoing inflammation. Dr. Corboy noted the lack of sufficient evidence, which is why he is conducting a PCORI/National MS Society-supported study called DISCOMS in people 55 or older, which will try to get evidence on when it is safe to discontinue therapy. This should help guide neurologists and people with MS on this important question. 
 
High Price of MS Therapies: In an invited talk to the general assembly of neurologists attending the AAN, Dr. Dennis Bourdette (Oregon Health & Science University) addressed what he called “The Elephant in the Clinic” – the skyrocketing costs of MS disease-modifying therapies, with prices that currently range from $62,000 to $92,000 per year.  He noted that these prices compel insurers to create impediments to coverage, which can harm people by delaying treatment. “We have an obligation to speak out on these issues,” he said. Dr. Bourdette is a member of the Society’s Advisory Committee on Access to MS Medications.
 

Restoring What’s Been Lost

Discoveries in the lab on approaches to repair nerve-insulating are making their way through clinical testing. Myelin repair is seen as a promising approach for restoring lost function and slowing down, or even stopping progression. At the same time, research is helping to advance strategies for addressing MS symptoms and to determine the extent that individuals’ behaviors, such as exercise and rehabilitation, can promote brain repair and brain plasticity.  

Phase 1 Stem Cell Trial Results: Dr. Saud Sadiq (Tisch MS Research Center of New York) and team reported results from an open label clinical trial involving 20 people with progressive MS, using individuals’ own mesenchymal stem cells (from bone marrow) to derive more specific stem cells called “neural progenitor cells.” The cells were expanded in the lab and then injected into the space around the spinal cord. The goal was to inhibit immune mechanisms and to augment tissue repair. Three doses were administered. The team reported mild to moderate headache as the most common side effect, and no serious adverse events.  At 3 months after the last dose, the team reported that half of those with bladder symptoms at baseline showed improvements. They also reported improvement in EDSS disability scores and walking speed, largely in people who were ambulatory at the start of the trial. The team intends to conduct a phase 2 trial of this therapy, and the Society is in discussions with the team to determine how best to support this important work. (Abstract P5.378)
 
Ampyra and Cognitive Impairment: Dalfampridine (Ampyra®) can enhance nerve conduction, and it was approved by the FDA for increasing walking speed. Additional studies to explore its impact on other MS symptoms have shown mixed results. Dr. Laura De Giglio (Sapienza University of Rome, Italy) and colleagues conducted a placebo-controlled clinical trial involving 120 people with MS and cognitive problems. After 12 weeks of treatment, significantly more of those on active therapy showed improvement in cognitive testing and fatigue. The trial was supported by Biogen. (Abstract S31.001)
 
Possible repair signal from “failed” trial? Last year, it was announced that a Phase 2 clinical trial of anti-LINGO (opicinumab), an approach to repair nerve-insulating myelin, did not meet its primary endpoint, which was improvement in measures of physical function (including walking, upper limb coordination), cognitive function, or disability. The trial involved 418 people with relapsing MS who were taking interferon beta-1a (Avonex) plus one of several doses of intravenous opicinumab or placebo for 72 weeks. Dr. Peter Calabresi (Johns Hopkins University) and others presented data teasing out responses in people given different dose levels, showing some evidence that one dose was better than the others. He noted that, based on a series of further analyses, an additional phase 2 trial will likely proceed. (Abstract S33.004)
 
Improving Walking/Preventing Falls: Canes, walkers and other devices can help keep people mobile but they can also sometimes increase the likelihood of falling. To investigate this problem, researchers led by Drs. Andrea Hildebrand, Michelle Cameron and colleagues (VA system, Oregon Health & Science University and other institutions) recruited 40 people with MS. Half of them were assigned to a waiting list and half received training in the use of their device for 6 weekly one-on-one sessions with a physical therapist. After 3 months, there were fewer falls in the group who received training than the wait-list group. The team hopes to repeat the study for a longer period of time with more people to help verify these findings. (Abstract 24.004)
 
Video Therapy for Hand Movement: Drs. Massimo Filippi, Maria Rocca and team (San Raffaele University, Milan) explored the use of video therapy – also known as “action observation training” – to improve hand function in people with MS. The idea is that watching a video of the action you want to improve activates brain circuits, and then physical therapy reinforces that activation to improve movement. The team did a study involving 41 people with MS who had disability in their right hands, and also in 46 people who didn’t have MS or hand problems. Half of each group received video therapy and physical therapy for hand movement (the active groups) and the other half received physical therapy but just watched videos of landscapes. The active groups received 10 sessions over 2 weeks. The team reported that video therapy improved hand function, especially strength, and caused associated changes in brain signals during hand movement as well. More study is needed to understand how to maximize potential improvements. (Abstract S43.002)
 

Ending MS

Although tremendous progress has been made in identifying key biological pathways that contribute to MS risk, the cause is still unknown. Preventing MS for future generations requires a deep understanding of what triggers MS, how triggers lead to the development of the disease, and how to protect against it. 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
 
Risk Factors for Developing Pediatric MS: Researchers from the National MS Society-supported Network of Pediatric MS Centers in the U.S. investigated potential links between viral infections and the development of MS in children and adolescents. They tested blood samples from 360 kids with MS and 496 kids without MS, looking for antibodies that would indicate exposure to Epstein-Barr virus, cytomegalovirus and herpes simplex virus. Infection with Epstein-Barr virus was strongly associated with higher risk of pediatric-onset MS. Their study, which is still being analyzed, is also exploring vitamin D levels and how infections interact with racial, ethnic and genetic factors. (Abstract S10.003)  Learn more about participation in this study

Ampyra is a registered trademark of Acorda Therapeutics, Inc.
 

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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