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April 25, 2019 News by Vijaya Iyer, PhD

Aubagio Lowers Relapse Rate in RRMS Patients, Real-world Observational Study Shows

In clinical practice, relapse events dropped by roughly half over a four-year period in relapsing-remitting multiple sclerosis (RRMS) patients treated with Aubagio (teriflunomide), a real-world study reports. The study, “Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study,” also examined patients’ perspectives in…

April 23, 2019 News by Ana Pena PhD

Study Will Explore Benefits of Tai Chi, Meditation on MS Patients’ Physical Balance

A pilot study has been launched to assess the immediate and enduring benefits of tai chi and mindfulness meditation on the physical balance and mental wellness of people with multiple sclerosis (MS). This community-based study — currently enrolling participants — is being conducted by the Motor Control Lab directed by Richard van Emmerik, PhD, professor of kinesiology at the University of Massachusetts Amherst. The project was awarded a $54,972 one-year grant from the National Multiple Sclerosis Society. While many MS symptoms vary from patient to patient, depending on the extent and location of the damage in the brain and spinal cord, difficulty in maintaining physical balance is a generalized complaint. Several MS symptoms can have an effect on balance, including difficulties with coordination, tremor and muscle weakness, stiffness, or dizziness and vertigo. "Mind-body interventions are beneficial as they train dynamic balance, such as transitioning between postures, turning, reaching, etc., in a manner similar to movements in daily life," Julianna Averill, a doctoral student at van Emmerik’s lab, said in a press release. Postural control and balance confidence is crucial to prevent patients' falls and reduce their fear of falling. Finding strategies that help patients cope and overcome this limitation is crucial, Averill noted. Contrary to other studies, which focus on mental health benefits, this project will look mostly at the effects of mindfulness practice on physical balance. Tai chi also will be evaluated for its potential to improve patients’ balance, both while they are standing and as they move. Participants will be randomly assigned to either eight weeks of free tai chi at YMAA Western Mass Tai Chi or mindfulness meditation classes at Downtown Mindfulness, in Hampshire County, Massachusetts. Tai chi is a Chinese martial art that involves body stretching and slow, focused, flowing postures that keep the body in motion. Mindfulness meditation is based on mindfulness practices, including training on body scan meditation, and loving kindness meditation. Participants will attend classes for 2.5 hours per week, where they will receive training to complete an additional 2.5 hours at home each week. At home, participants are asked to listen to meditation podcasts, or watch tai chi videos via a website that also tracks their activity. “The participants will be trained, and they will be able to practice on their own,” Averill said. Patients' postural sway will be recorded by wearable sensors while performing distinct movements at the study start, at the end of all classes, and two weeks later. On the same visits, participants will be surveyed to assess the frequency of falls, balance confidence, level of fatigue, and ability to cope and adapt. “We’re taking a more holistic look, considering the whole person and overall quality of life,” Averill said. The team plans to enroll 30 participants with mild-to-moderate MS symptoms, aged 21 to 70, and who are able to stand and move without assistance for 15 minutes. For more information about the study and how to participate, contact Averill at [email protected].

April 18, 2019 News by Patricia Inacio, PhD

Oligodendrocyte Precursor Cells Disrupt Blood-brain Barrier, Trigger Brain Inflammation in MS, Study Shows

Oligodendrocyte precursor cells (OPCs), the cells responsible for myelin production, are unable to migrate into sites of myelin loss in the brain. These cells then cluster and disrupt the blood-brain barrier (BBB), triggering an inflammatory process in the early stages of multiple sclerosis (MS), a study shows. The study, “Aberrant oligodendroglial–vascular interactions disrupt the blood–brain barrier, triggering CNS inflammation,” was published in the journal Nature Neuroscience. MS is an autoimmune disease characterized by the loss of myelin (demyelination) — the fat-rich substance that protects nerve fibers — which leads to neurodegeneration. Along with loss of myelin, researchers have observed that the blood-brain barrier — a highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation — breaks down in the initial stages of disease. A team led by researchers at the University of California, San Francisco, have now discovered that OPCs are involved in the disruption of the blood-brain barrier in MS, according to a press release from the National MS Society, which funded the study. Oligodendrocytes are myelin-producing cells and are responsible for myelinating the nerve cells’ axons — a single oligodendrocyte is capable of myelinating multiple axons. Mature myelin-producing oligodendrocytes develop from more immature, stem cell-like OPCs. In a normal brain, upon myelin loss, OPCs are called into action and travel into the damage site where they mature and generate myelin-producing oligodendrocytes. In this study, the researchers found that OPCs in MS form clusters in blood vessels of the brain-blood barrier, having lost the ability to detach from these vessels and migrate to injury sites. In an animal model of MS, they saw that OPC aggregates altered the location of other cells — called astrocytes — in a competition for space, and contributed to the disruption of blood vessels. Astrocytes are a group of star-shaped cells, belonging to the group of glial cells, that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation. The team also observed that OPC aggregates trigger an immune inflammatory response, shown by a large number of microglia (the central nervous system immune cells) and immune cells called macrophages around these cell clusters. “We find in several MS cases, in lesion areas with active inflammation, that OPCs can be found clustered on vasculature, representing a defect in single cell perivascular migration and inability to detach from blood vessels,” the researchers wrote. Further molecular analysis revealed that OPCs have high levels of Wnt signaling, and elevated secretion of Wif1 factor to the extracellular space that could explain why OPCs accumulate and destroy the blood-brain barrier. The WiF1 factor is actually a negative regulator of Wnt signaling that is essential for the maintenance of the blood-brain barrier structure. This factor competes with Wnt ligands, and affects the integrity of cellular junctions, making the blood-brain barrier more fragile and permeable. "Evidence for this defective oligodendroglial–vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB,” the researchers wrote. They suggested that more studies are needed to better understand the interactions between blood vessels and oligodendrocytes, which could help identify new therapeutic targets for promoting myelin repair in MS.

April 12, 2019 News by Marisa Wexler, MS

Excess Body Fat Spurs Disease Progression by Impact on Immune Cells, Study Suggests

A link between fat molecules called ceramides and worsening disease in overweight and obese people with multiple sclerosis appears to exist, a study reports, with its findings suggesting that ceramides prompt the growth of immune cells called monocytes, which in turn spurs disease progression. These results also strengthen the likelihood that lifestyle factors, like diet and weight, can act as disease modifiers, its researchers said. High body mass index has been linked to the risk of developing MS, but for reasons that aren't clear. One idea is that weight-induced differences in lipids (fat molecules) in the blood, because they are involved in several cellular signaling processes, may affect MS and its course in people with higher BMIs. To test this hypothesis, a team led by researchers at the Advanced Science Research Center (ASRC) at The Graduate Center and at the Icahn School of Medicine at Mount Sinai analyzed 54 patients with relapsing-remitting MS (MS), ages 18 to 60, and with normal or high BMIs (27 people in each group). Participants were followed for two years. BMI is a measure of body fat based on height and weight. A normal BMI is defined as one between 18.5 and 24.9, while a person is considered overweight with a BMI of 25–29.9, and obese it is 30 or higher. Researchers took blood samples, and looked for differences between the groups in terms of both immune cells and blood lipid profiles. They then validated their findings in a separate group of 91 RRMS patients. Patients with high BMIs tended to have more monocytes than those with normal BMIs. Monocytes can travel through the blood to tissues where they develop into macrophages, immune cells with various functions that are best known for "eating" invading bacteria. Monocytes can also travel to the brain and damage nerve fibers. Overweight and obese patients also had significantly higher levels of ceramides compared with normal-weight patients, and the researchers wondered if a link might exist between the two. Through a set of experiments in cells, they discovered that ceramides cause epigenetic changes in monocytes; that is, they alter the way their genomes are "read," so they alter gene activity. Specifically, ceramide-treated cells showed a type of epigenetic change called methylation — which generally turns genes "off" — in genes that normally help prevent cells from dividing. Conceptually, these genetic changes serve to unleash monocytes, leading them to grow more (proliferate) than they otherwise might. The researchers also found more methylation on the genomes of monocytes from high-BMI patients than those from low-BMI patients, and they noted that the overweight or obese patients also tended to have greater disease activity, worse disability progression, and more brain lesions on MRI (magnetic resonance imaging) scans on follow-up. Finally, the researchers tested a mouse model of MS, giving one group of mice a standard diet and another a high-fat diet. Mice fed the high-fat diet were found to have greater disease severity, more brain lesions, and more monocytes, confirming the findings seen in MS patients. "This study gives us a much-needed view into the environmental influences that can affect and change the behavior of cells in an individual's body," Kamilah Castro, the study's first author, said in a press release. "Our findings suggest that increased levels of saturated fat as a result of dietary habits are one likely cause of the epigenetic changes that advance MS, which gives us a starting point for a potential intervention." According to the team, the findings support the concept of nutri-epigenomics: that is, the ability of food to alter the way the genetic information is interpreted by each cell, and suggest that "weight management and dietary intervention" might affect MS prognosis. One limitation was the study's small size, its researchers noted. "While we consider our results … very exciting and mechanistic, we acknowledge that the potential consideration of ceramide levels as biomarkers for disease progression in MS would require validation ... using larger cohorts with a longitudinal and/or cross-sectional design," they concluded. "It will also be important to evaluate the effectiveness of dietary intervention (with an emphasis on the reduction of specific classes of saturated fats), as potential modulator of plasma ceramide levels and possibly of disease course in MS patients."

April 8, 2019 News by Jose Marques Lopes, PhD

Mayzent ‘Will Change Lives’ of MS Patients Transitioning to SPMS, Novartis Says

The “regulatory environment” favored Mayzent (siponimod) being approved as an oral treatment for people with relapsing multiple sclerosis (MS) — specifically, clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive MS (SPMS) — a top executive with Novartis said, although the pharmaceutical company had requested a label covering all with SPMS. Dan…

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