Reports of Progress and Challenges from ECTRIMS, World’s Largest MS Science Meeting - National Multiple Sclerosis Society

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Reports of Progress and Challenges from ECTRIMS, World’s Largest MS Science Meeting

October 17, 2013

This year’s European Committee for Treatment and Research in MS (ECTRIMS) meeting hosted nearly 8,000 participants in Copenhagen, Denmark, from around the world. They gathered to share ideas and communicate new findings to stimulate faster progress in MS research.

Anyone interested in ECTRIMS presentations can visit the meeting Website and view the scientific summaries (referred to as abstracts in the program). If you register, you may also access their online library of recorded presentations.

Also available are blogs from scientist/journalist Dr. Julie Stachowiak, who lives with MS, and Society research staff Drs. Timothy Coetzee, Nicholas LaRocca and Bruce Bebo.

In addition, below is a summary of just a few of the 1,000 presentations and posters on research focusing on cutting-edge research addressing virtually every aspect of the challenge to stop MS in its tracks, restore function, and end MS forever.

STOP -- TherapiesResearch -

In the opening ECTRIMS lecture, Dr. Giancarlo Comi of the Università Vita-Salute San Raffaele in Milan discussed the increasing evidence that treatment with disease-modifying therapies early in the course of MS can help prevent future loss of function. He noted that as the ability of physicians to identify MS in its earliest stages improves, there may be opportunities to treat the disease earlier and improve outcomes for people with MS. (Abstract 81)

Available therapies: There were numerous additional reports supporting the benefits of many of the approved therapies for relapsing MS, and first results from the international phase 3 TOPIC trial of oral teriflunomide (Aubagio,® Genzyme, a Sanofi company) in people who had clinically isolated syndrome or CIS, a situation where a person experiences a first neurological event that often, but not always, progresses to definite MS. Compared to those on placebo, daily (14mg) Aubagio reduced the risk of converting from CIS to definite MS by 42.6%, and reduced the risk of experiencing a new relapse or new lesion seen on MRI by about 35%. The most common adverse events were elevated liver enzymes, headache, hair thinning, diarrhea, and paresthesia (burning or prickling sensation). (Abstract 99)

Pipeline therapies: There were many presentations about new therapies in the pipeline and looking at new ways to analyze data from clinical trials completed or in extension phases. These included alemtuzumab and peginterferon beta-1a (both being reviewed by the U.S. FDA), laquinimod, ocrelizumab and daclizumab.

Neuroprotection: The idea of protecting the nervous system from damage in MS was a major topic, and one approach is to test therapies already on the shelf for their protective qualities. It was disappointing to learn that a small clinical trial of the ALS therapy riluzole, conducted by Dr. Emmanuelle Waubant at the University of California at San Francisco with Society funding, failed to show benefits. The team learned some valuable lessons in terms of trial design that will be helpful for future studies of this type. While this one result is disappointing, additional neuroprotection trials are underway. (Abstract 234)

Progressive MS: During a session devoted to progressive MS, Dr. Robert Fox of the Cleveland Clinic discussed several key initiatives underway to address the challenges presented by these forms of the disease. One focus was the Progressive MS Alliance, an international effort to connect resources and experts around the world to find the answers and develop the solutions to end progressive MS. (Abstract 195) Some 85 separate presentations at ECTRIMS specifically referenced progressive MS, and many others focused on issues that have direct bearing on this form of the disease, suggesting that more attention is being paid to understanding, stopping and reversing progression.

STOP -- Understanding MS Damage

There were many reports of progress in understanding what drives myelin destruction and nerve degeneration in MS, which are key factors underlying progressive forms of the disease.

Racial differences: Dr. D. Kimbrough and colleagues from across the U.S. investigated eye health in 698 people with MS and 137 participants without MS. At the outset of the study, among healthy participants the nerve fiber layer in the back of the eye (retinal fiber layer) tended to be thicker in African Americans than in Caucasians, but this difference was not seen in people of either race who had MS. Later (ranging from 6 months to over 3 and a half years) the nerve fiber layer of African Americans with MS had thinned much more than that of Caucasians, and there was more vision loss among African Americans with MS who had a history of optic neuritis compared to Caucasians. This adds to previous studies suggesting that MS may be more aggressive in African Americans. (Abstract 60)

MS lesions: Dr. Bruce Trapp of the Cleveland Clinic showed that new MS lesions undergo natural repair of nerve-insulating myelin much better than older (“chronic”) ones, and that cells capable of making new myelin are in chronic lesions but they are stalled. His team has found MS lesions that straddle two different parts of the brain – the white matter and the gray matter. The team found that chronic lesions in the white matter (contains a lot of myelin and the lesions can be seen on a standard MRI scan) don’t remyelinate. But chronic lesions in the gray matter (has less myelin and the lesions cannot be seen on an MRI scan), show robust remyelination – even in people living with MS into their 70’s. Dr. Ranjan Dutta and others of the team are comparing differences on a molecular level in the two regions to figure out how to make the white matter repair like the gray matter. (Abstract 218)

Energy crisis: There is increasing evidence that malfunctions of mitochondria, the tiny energy producers of cells (like battery packs), contribute to nervous system damage in MS. Dr. Martin Kerschensteiner of Ludwig-Maximilians-University in Munich, Germany presented amazing pictures showing the movement, or “trafficking,” of substances and mitochondria inside living nerve cells. He also showed how movement can be blocked. Using this technology the team is tracing how nerve cells are damaged in MS, and have uncovered signs that for certain damage, the nerves will either recover fully or degenerate. This work provides a basis for a more targeted approach to strategies for preventing the nerve degeneration that underlies progressive MS. (Abstract 83)

Toxic factors: Recent research points to a previously unsuspected role of immune B cells in MS disease activity, and clinical trials of treatments that target B cells (such as ocrelizumab) are underway. Drs. Robert Lisak (Wayne State University, Detroit), Amit Bar-Or (Montreal Neurological Institute) and team wanted to see whether these cells release substances that are harmful to nerve cells grown in lab dishes. They took B cells from the blood of 7 people with relapsing MS and 8 people without MS and let them grow in lab dishes, then collected the liquid they grew in, diluted it and added it to neurons. They found that the B cell products from people with MS were significantly more toxic to nerve cells than that from controls, adding evidence to the idea that B cells may be important players in nervous system damage in MS. (Abstract P816)

Iron deposits: Previous studies have shown that iron is deposited in some MS brain lesions, but its source and role have been unclear. Iron is critical normal cell function, and it is released when cells are damaged. Drs. S. Hametner and Hans Lassmann of the Medical University of Vienna, and team members in Austria and Germany, reported that in MS iron is released from the myelin producing cells that are dying as a consequence of MS immune attacks. This released iron is picked up by other brain cells, which may cause those cells to degenerate via a process known as oxidative damage. This supports the idea that damage to myelin making cells during the first waves of MS attacks release substances, including iron, that may trigger the more progressive and neurodegenerative phase of MS. (Abstract 50)

RESTORE – Myelin Repair

In 2005 the National MS Society made significant investments into nervous system repair and protection research – and we continue to see some promising results. People are excited by the possibility, once only a dream, that we will find a way to repair damaged myelin. This is important not only for restoring  function, but many believe that re-establishing the protective myelin coating on axons will shield them from further harm.

There are now immune-based therapies that can help control relapsing forms of disease for many people. While researchers continue to look for ways to improve the treatment of relapsing MS, the focus in MS research is shifting to discovering strategies that stop MS progression and repair the damage that causes disability. This has relevance to people with all types of MS, but especially people with progressive MS.

Myelin repair: Dr. Larry Sherman of Oregon Health and Science University reported that fragments of a molecule called hyaluronic acid (HA for short) accumulate in chronic white matter lesions and could be at least partially responsible for the stalled myelin repair. They have identified an enzyme that chews up the HA into fragments and have shown that inhibitors of this enzyme promote myelin repair. They are now trying to figure out exactly how this works in hopes of developing treatments that help restore function in MS. (Abstract 212)

Cell therapy: Another strategy to repair myelin in MS is to introduce new repair cells into the system via transplantation. Of note was a report by Drs. C. Laterza, Gianvito Martino and colleagues from San Raffaele Scientific Institute in Milan who used mouse skin stem cells and forced them to become myelin-making cells. As in previous studies of this type, after these cells were infused into the spinal cord, they promoted recovery in mice with the MS-like disease EAE. The team showed that these cells didn’t actually make myelin themselves, and they’re starting to identify the growth factors they release, which stimulate natural repair and also reduce inflammation. More work is needed, but this type of research gives hope that this strategy may eventually help restore lost function. (Abstract 173)

Repair trials: Updates on two repair therapies already being tested in human clinical trials were presented. The first is called anti-LINGO. LINGO is seen in neurons and myelin-producing oligodendrocytes, and blockading this protein with anti-LINGO has been shown to promote remyelination in animal models. Biogen Idec reported that anti-LINGO was well tolerated in people and that no negative effects were seen in the nervous system using MRI scans. This means the company will likely keep pursuing clinical development of this promising repair candidate. (Abstract P545)

Investigators from the Mayo Clinic are developing an agent called rHIgM22 that has been shown to promote extensive remyelination in several different animal models of MS. Early research on this approach, now in early clinical trial testing, was supported by the National MS Society. (Abstract P1194)

Sex hormones: While originally studied for their anti-inflammatory activity, increasing evidence suggests that female sex hormones might be protective of the nervous system or even promote repair of myelin. ENDECE Neural reported that NDC-1308 has shown promise in mice with an MS-like disease, reducing disease activity and stimulating myelin repair. (Abstract 209) Another estrogen-related compound in development by KaroBio, KB3944, is being explored for its ability to increase the number of myelin-making cells in lab models. (Abstract P430) The National MS Society through Fast Forward is supporting further development of both of these approaches. (Read more)

RESTORE – Exercise therapy and rehabilitation

Mounting evidence suggests that exercise and rehabilitation can help many levels of function and quality of life for people living with MS. The annual Conference of Rehabilitation in MS was held jointly with ECTRIMS, enabling researchers to share creative strategies to study and maximize the potential benefits of rehabilitation and exercise to address MS.

Benefits: Some of these strategies were described by Dr. Ulrik Dalgas of Aarhus University, Denmark, who reminded the audience that for many years people with MS were advised against exercising because it seemed to make fatigue and other symptoms worse. Thanks to research, we now know that this worsening is usually temporary and outweighed by the benefits. There have been hints that exercise can fight depression and improve cognition, and possibly even modify disease activity. The extent of these benefits and the optimal type of exercise for these benefits needs further study. (Abstract 128)

Incorporating activity into daily life: National MS Society-funded researcher Dr. Robert Motl of the University of Illinois at Urbana-Champaign discussed the fact that fewer than 20% of persons with MS engage in sufficient physical activity, and that over half of adults drop out of formal exercise programs after only 3 months. He also discussed potential ways for people to incorporate more physical activity into their daily lives – something called “lifestyle activity.” He noted studies suggesting that such intermittent exercise can accumulate during the day to have the same effect as continuous exercise. (Abstract 129)

Building the brain: Dr. L. Prosperini and colleagues from Sapienza University of Rome had previously reported that an intensive home-based training program using the Nintendo Wii balance board improved standing balance and inhibited swaying in people with MS. Finding a way to improve balance can prevent falls. Falls and fear of falling can dramatically impact a person’s quality of life.

The team did advanced brain imaging in 21 people before and after a 12-week training period with the Wii board. After the training, differences in the imaging suggested that myelin in some parts of the brain had gotten thicker, particularly in the part that controls movement and balance (cerebellum). More work is needed, but this adds to evidence that specific exercise and rehabilitation may alter the brain.  (Abstract 164)

Kaatsu resistance training: A novel approach called kaatsu resistance training is based on the idea that people who are already weak may have a hard time exercising with enough vigor to see positive changes in strength or growth in muscle mass. Dr. Y. Learmonth and others at the University of Illinois at Urbana-Champaign presented preliminary results of kaatsu training, in which blood flow to the muscles is partially blocked by a device similar to a blood pressure cuff, while performing lower limb exercises such as leg presses and curls. This may simulate extra resistance so that the exerciser needs to use less force to achieve gains. Eight people did these exercises 3 times a week for 6 weeks – 4 with the kaatsu cuff and 4 without. This was a small study, but they found it to be safe and also found hints that those using the cuff showed more signs of improved strength than the control group who didn’t use the cuff.  (Abstract P1184) The National MS Society is now funding a small pilot study to further explore its potential.

END MS FOREVER – Risk Factors

Researchers continue to identify some factors that may contribute to MS, such as specific genes, infections, and lifestyle factors such as smoking and obesity. None of these is a single cause of the disease, and it’s clear that not everyone who has MS has been exposed to these factors, and not everyone who is exposed to them will get MS. But furthering our understanding of possible contributors will help us figure out what causes MS.

MS risk genes:  National MS Society research fellow, Dr. Nikolaos Patsopoulos of Harvard, received an ECTRIMS Young Investigator award for an oral presentation of a study by the International MS Genetics Consortium that maps common gene variations related to susceptibility to MS. Many are involved in immune functions. These findings do not substantially improve the ability to provide genetic counseling to individuals, but should add knowledge about complex biological pathways that lead to the development of MS. (Abstract 90) (Read more)

Twins and genes: Dr. Helga Westerlind of the Karolinska Institute reported on a study by a team taking advantage of MS patient registries in Sweden, one of which dates back to the 1800’s. They took a fresh look at how much having a family member with MS increases a person’s chances of getting the disease, and they focused on identical and fraternal twins. Comparing the risk of these two groups is important because identical twins are thought to share the same genes whereas fraternal twins do not. They found that the risk of an identical twin getting MS if the other twin has the disease was lower than in prior reports, but still much higher than in fraternal twins. This study suggests that that the role of genes may be more complicated than previously suspected. (Abstract 57) (Read more about genetic risks)

Interaction of risks: The incomplete picture of risk genes is driving more studies looking at their interaction with a person’s environment and lifestyle. For example, Danish researchers Dr. A.B. Oturai and colleagues from Copenhagen University looked at a group of potential risk factors, including known MS susceptibility genes, obesity in early adulthood, previous mononucleosis and high teenage alcohol consumption. They found that each of these factors contributed to lowering the age at which an individual was diagnosed with MS. (Abstract 120) A related study suggested that preventing teen obesity in people with MS susceptibility genes may reduce their risk of developing MS. (Abstract 134)

Smoking: In a large population study, Dr. A.K. Hedström and team from the Karolinska Institute in Stockholm confirmed that cigarette smoking increased the risk for developing MS at any age, and climbed with the amount smoked. They also found that quitting smoking completely reversed the risk back to normal within a decade. (Abstract 118)  The same team reported that smoking could increase a person’s risk of developing the kind of antibodies in their blood – called neutralizing antibodies – that can block the ability of interferon beta to reduce MS disease activity. (Abstract P1099)

Dietary salt: Recent studies have pointed to salt intake as a possible risk factor for developing MS or for making mice with MS-like disease worse. New evidence presented this week by Dr. M.F. Farez and colleagues at the Institute for Neurological Research in Buenos Aires and Boston suggest that high salt intake may also increase MS exacerbation rates and MRI-detected disease activity in people who have the disease. Further, larger studies are needed to confirm these results. (Abstract 119)

Gut microbiome: Another emerging area of research is the gut microbiome – colonies of trillions of bacteria that inhabit our intestinal tracts, most of which are beneficial. The immune activity that occurs in the gut and which is related to the immune system, may help dictate other aspects of health, including the activity of an individual’s MS. A lecture by Dr. O. Borbye Pedersen of the University of Copenhagen made it clear that this is a very promising field of study. If we could decipher the influence of the gut microbiome, we have the potential of altering it to treat or even prevent MS.  (Abstract 219)

Viruses: Infectious disease specialist Dr. Julian Gold of Sydney, Australia and Barts and the London School of Medicine and Dentistry presented an overview of research on whether viral infections trigger or cause MS, the conflicting results, and the fact that it is technically difficult to isolate a specific virus in the brain and attribute it as a cause. He also cited some research suggesting that the genetic material from “human endogenous retroviruses” makes up a portion of the entire complement of human genes and could play a role in triggering immune attacks. He looked at health registries and searched the literature to find that few people who are treated with anti-retrovirus therapy to treat HIV have been reported to have MS. Based on these ideas, a group has launched a small pilot trial, called INSPIRE, to see whether brief treatment with the anti-viral therapy raltegravir can alter brain MRI in people with relapsing MS. (Abstract 115) (Read more about viral triggers)

Vitamin D: Dr. Alberto Ascherio of Harvard School of Public Health, with an international team of collaborators, were able to study blood draws that had occurred during the phase 3 BENEFIT trial that studied the impact of early versus delayed treatment with interferon beta-1b in people who had “clinically isolated syndrome,” a first neurological event that often progresses to definite MS, but not always. The team wanted to see whether the concentrations of 25-hydroxyvitamin D (which indicates vitamin D status) in the serum could predict whether a person would develop definite MS. They found that people with low vitamin D levels early on were more likely to develop definite MS and to have more disease activity, whereas those with higher levels early on had fewer brain new active lesions seen on MRI and lower relapse rates and less disease progression 4 years later. (Abstract 96)

Several new clinical trials are getting underway to test whether increasing an individual’s vitamin D levels can delay the development of MS. And the National MS Society is supporting a trial to see whether vitamin D supplements can reduce MS activity in people already diagnosed. (Read more on vitamin D)

This is just a taste of the many, many reports of progress and challenges from a worldwide community of scientists and doctors searching for ways to stop MS, restore function and end MS forever.

Aubagio is a registered trademark of Genzyme, a Sanofi company.





About Multiple Sclerosis

Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts 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 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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