Deregulated RNA Molecules May Contribute to RRMS, Study Finds

The levels of three small, regulatory RNA molecules — long non-coding RNAs — are deregulated in blood samples of patients with relapsing-remitting multiple sclerosis (RRMS), a study reports. The long non-coding RNAs are involved in the regulation of the natural immune response and DNA-damage response, supporting the theory that these…

Smoking Increases Relapse Rate in RRMS Patients on Tysabri, Study Suggests

Smoking increases the relapse rate in patients with relapsing-remitting multiple sclerosis being treated with Tysabri , an observational study suggests. Multiple sclerosis is a multifactorial disease associated with both genetic and environmental risk factors. Smoking, in particular, has been linked to numerous aspects of MS, including its development and progression. In a previous study, the research team looked at how smoking influences the relapse rate in RRMS patients being treated with interferon beta. From more than 800 patients, they found that smoking one pack per day (about 20 cigarettes) essentially interfered with the positive effect of the IFN-beta treatment and increased the relapse rate by 27%. The researchers then questioned whether the same was true for other treatments. Tysabri, developed by Biogen, is a monoclonal antibody that targets the alpha-4 integrin protein. By interfering with this molecule, the therapy prevents white blood cells from moving into the central nervous system, suppressing the immune reaction that contributes to MS symptoms. In the study, 355 Tysabri-treated RRMS patients from the Danish Multiple Sclerosis Centre were assessed. To gather information on smoking habits and body mass index, the patients filled out a 100-question survey. Data was collected between the start of the treatment and a two-year follow-up visit. Results showed that smoking one pack of cigarettes per day increases the relapse rate by 38% in RRMS patients on Tysabri. This increase in relapse rate takes into account both sex and age at the start of treatment, since age can affect the relapse rate. For example, an increase in age by one year raises the number of relapses by 2%. The researchers also looked at the relationship between smoking and the presence of two immune-related alleles: HLA-DRB1*15:01 and HLA-A*02:01. Previous studies showed that HLADRB1*15:01 is associated with an increased risk of developing MS, while HLA-A*02:01 is linked to a decreased risk. Although previous studies reported a link between smoking and these two alleles in MS patients, the current study did not find an association between smoking and carrying either of these alleles. Based on the results, the researchers concluded that smoking significantly increases the relapse rate in RRMS patients receiving Tysabri. According to the team, the results "add important information that hopefully will sharpen the focus on the overall harmful effects of smoking in MS patients."

African-Americans Show Better Adherence and Satisfaction with Gilenya Than Injectable DMTs, Phase 4 Study Finds

African-Americans with relapsing–remitting multiple sclerosis (RRMS) show higher adherence and greater satisfaction when treated with oral Gilenya (fingolimod, by Novartis) than with injectable therapies, according to a new study. The research, “Treatment retention on fingolimod compared with injectable multiple sclerosis therapies in African-American patients: A…

Progressive MS Patients with Considerable Disability Ably Treated with Cladribine, UK Case Study Reports

Cladridine may be effective in preventing disability progression and reducing damage to nerve cells in people with progressive forms of multiple sclerosis (MS), researchers suggest based on a case study of two such patients given the injectable treatment. MS is characterized by progressive degeneration of cells in the central nervous system, mostly…

Missouri Trial to Examine if Fasting Alters Gut Microbiome and Immune System of RRMS Patients in Helpful Ways

A 12-week clinical study is recruiting people with relapsing-remitting multiple sclerosis (RRMS) to evaluate if intermittent fasting can improve their immune response, metabolism, and gut microbiome — the bacterial community that inhabits the gastrointestinal tract. Its findings may also hint at whether such a diet might ease MS symptoms or alter discourse course and, if used in conjunction with other treatments, boost their efficacy. Conducted by researchers at Washington University in St. Louis, Missouri, the trial is supported by their findings in an earlier mouse study.  Results showed that fasting worked to ease MS-like symptoms in a mouse model of the disease, the research team reported. Specifically, EAE mice fed every other day were less prone to symptoms that included difficulty in walking, limb weakness, and paralysis than mice allowed to eat freely.  A fasting diet also enriched bacterial diversity in the mice guts, and shifted immune cell populations there toward a lower inflammatory response. When gut bacteria were transferred from fasting mice to nonfasting mice, the later also were seen to be better protected against MS-like movement problems, supporting the influence of the gut microbiome on MS symptoms. Several diets have been proposed to help ease disease progression in MS patients, but solid scientific evidence is lacking to support any one diet over another, leaving the issue much to an individual’s choice. “The fact is that diet may indeed help with MS symptoms, but the studies haven’t been done,” Laura Piccio, MD, an associate professor of neurology at WUSTL and the study's lead author, said in a WUSTL news release written by Tamara Bhandari. Taking place at the Missouri university, the trial is expected to enroll 60 RRMS patients. Half will be randomly assigned to eat a standard Western-style diet seven days a week, and the other half to Western-style diet five days a week, with two days set aside for fasting (consuming a maximum of 500 calories each day). On fasting days, patients can only drink water or calorie-free beverages and eat fresh, steamed or roasted non-starchy vegetables All will undergo a neurological assessment, and provide blood and stool samples in the study's beginning, at mid-point or week six, and at its end (week 12). Those using MS medications will continue on their prescribed treatment regimens throughout the study. More information, including enrollment information, is available here. Piccio noted that a pilot study on diet in 16 MS patients showed that limiting calories every other day for two weeks led to immune and gut microbiome changes that resembled those observed in the mice study she helped to lead. Its researchers concluded that intermittent fasting had the potential to positively manipulate the immune response in MS patients by changing their gut microbiome. The gut microbiome plays a central role in digestion, and in producing vitamins and amino acids (the building blocks of proteins). But a growing body of evidence indicates that it also determines how our immune systems develops and matures. Indeed, an increasing number of studies link irregularities in the gut microbiome with MS. “There are several possible ways fasting can affect inflammation and the immune response,” Piccio said. “One is by changing hormone levels. We found that levels of the anti-inflammatory hormone corticosterone were nearly twice as high in the fasting mice. But it also could act through the gut microbiome.” The new trial will allow the team to analyze more deeply the effects of a fasting diet — and perhaps gather evidence for a larger study investigating if skipping meals can ease MS symptoms. Its goal is to find out "whether people on limited fasts undergo changes to their metabolism, immune response and microbiome similar to what we see in the mouse,” Piccio said. “I don’t think any physician working with this disease thinks you can cure MS with diet alone,” she added, “but we may be able to use it as an add-on to current treatments to help people feel better.”

#CMSC2018 – Gains in Functional Abilities Seen in Lemtrada-treated MS Patients Over Six Years, CARE-MS II Extension Study Shows

Patients with active relapsing-remitting multiple sclerosis (MS) continue to show improvement — lesser functional disability across a variety of measures — and often without the need for continuous treatment after taking Lemtrada for two years, according to six-year results from the CARE-MS II extension study. These results were shared in a…

GeNeuro-Servier Antibody Limits RRMS Patients’ Brain Shrinkage, Phase 2b Trial Shows

The laboratory-generated antibody GNbAC1 continued to limit brain shrinkage a year after relapsing-remitting multiple sclerosis patients began receiving it, its developers announced. GeNeuro and Servier were reporting on the 12-month results of a Phase 2b clinical trial. GNbAC1 is a monoclonal antibody that destroys a harmful retroviral protein called pHERV-W which scientists have…

Smoking Increases Relapses in RRMS Patients Receiving Interferon-beta, Study Suggests

Cigarette smoking increases the relapse rate in patients with relapsing-remitting multiple sclerosis who are being treated with interferon-beta, a study suggests. The findings suggest that RRMS patients who smoke may have fewer relapses if they quit. An article on the results, “Smoking affects the interferon beta treatment response in multiple sclerosis,” appeared in the journal Neurology. A number of studies have looked at the link between environmental and lifestyle factors and the risk of developing MS. These factors include how much sunlight and vitamin D patients get and whether they have an Epstein-Barr virus infection. Cigarette smoking is a well-documented risk factor in MS, but most of the studies on it have focused on the link between smoking and MS, or the link between smoking and the  disease's progression. “Studies that addressed the relationship between smoking and disease activity in RRMS are rarer,” the researchers wrote. The team decided to investigate whether smoking during interferon-beta treatment would affect relapse rates. Previous research had set the stage for the study by showing a link between smoking and gene mutations that make people more susceptible to developing MS. The mutations were in the HLA and NAT1 genes. The team looked at DNA from 834 RRMS patients in the Danish Multiple Sclerosis Biobank who were treated with interferon-beta. Well-known brand names of the treatment include Rebif, Avonex, and Plegridy. There are also other brand names and biosimilar drugs. Researchers also looked at patients’ medical records two years before they started on interferon-beta. Before making any conclusions on possible links between smoking and patients' relapse rate, the team adjusted for patients’ sex, age at the start of treatment, and number of relapses in the two years before treatment began. Their key conclusion was that smoking increased by more than a quarter the number of relapses in patients on interferon-beta therapy. “Each pack of cigarettes more per day during IFN-β [interferon-beta] treatment increased the number of relapses by 27%,” the team wrote. The researchers found no association among smoking, relapses, and mutations of the HLA or NAT1 genes. “Our results confirm that lifestyle factors are important in MS, suggesting that smoking cessation may be associated with a reduction in disease activity,” they wrote. “Although not formally proving that smoking cessation will decrease disease activity in RRMS, the results should encourage physicians to inform patients with MS about the harmful effect of smoking and increase focus on smoking cessation,” they observed.