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February 12, 2019 News by Alice Melão, MSc

Direct Nerve Stimulation Using MyoRegulator System Seen to Reduce Spasticity in Mice with Spinal Injury

Treatment with PathMaker Neurosystems’ anodal trans‐spinal direct current stimulation (tsDCS), a non-invasive direct nerve stimulation tool called MyoRegulator, was found to effectively ease spasticity in mice with spinal cord injury, a study reports. A link between the ability to control muscle contraction and the levels of a specific neuronal…

February 8, 2019 News by Jose Marques Lopes, PhD

Medicare Rules, Higher Cost-sharing Load Increase Out-of-pocket Spending for MS Therapies, Study Reports

Restrictive access policies by Medicare and a rising cost-sharing burden lead to an increased price of disease-modifying therapies for multiple sclerosis patients, according to new research. The findings also revealed that Medicare beneficiaries without a low-income subsidy may spend on average $6,894 for their MS treatments in 2019, with generic versions of Copaxone representing the highest burden. Approximately 25-30% of patients with MS are covered by Medicare through disability. In 2013, MS Medicare beneficiaries with MS and without low-income subsidies averaged $4,389 a year in out-of-pocket expenses, second only to hepatitis. Despite a greater number and diversity of DMTs for MS treatment, their price has increased substantially over the past two decades. In fact, expenses related to DMTs for MS are among the highest by class in the Medicare market. “It’s a dysfunctional market that lacks the typical incentives for most other consumer prices,” Daniel Hartung, the study’s lead author, said in an Oregon Health & Science University (OHSU) press release written by Erik Robinson. “Aside from the public optics, there are few incentives for companies not to raise prices. Most intermediaries in the drug distribution channel, including drug companies, benefit from higher prices,” Hartung said. These high prices may lead to reduced access, as insurance companies can restrict coverage or manage use through prior authorization or step-therapy policies, and high deductibles or cost-sharing components in health plans that increase the financial burden for patients. Now, a team at OHSU and the Oregon State University College of Pharmacy used prescription drug plan formulary files to analyze changes in coverage policies from 2007 to 2016, and to estimate out-of-pocket spending for DMTs for MS within Medicare Part D program, through which outpatient prescriptions are financed. Eleven DMTs available during the study period were analyzed. Tysabri and Lemtrada were not part of the analysis because they are delivered via intravenous infusion in the clinic setting, and are typically covered through Medicare Part B. Results revealed that the price for Betaseron , Copaxone 20 mg , Rebif, and Avonex — the four therapies available in 2007 — quadrupled over the 10-year study period. Except for Copaxone 40 mg and its 20 mg generic formulation (Glatopa, by Sandoz), prices for the other DMTs introduced after 2007 increased by 9–13% per year. These include Novartis’ Extavia (interferon beta-1b) and Gilenya (fingolimod), Biogen’s Plegridy (peginterferon beta-1a) and Tecfidera (dimethyl fumarate), and Sanofi Genzyme’s Aubagio (teriflunomide). In 2007, 99-100% of plans covered the four available medications, with the exceptions being Rebif (88%). These percentages fell to 54-89% in 2016. Coverage of the other DMTs varied between 21% (Extavia) to 92% for Copaxone 40 mg. In turn, coverage for the three oral options — Gilenya, Aubagio and Tecfidera — generally increased or was maintained over time, ranging from 46% for Aubagio to 83% for Gilenya. The use of prior authorization increased from 61-66% in 2007, to 84-90% in 2016. Also, the share of plans with at least one DMT available without limitations declined from 39% to 17%. The average projected out-of-pocket spending for 2019 across DMTs was $6,894. The highest projected out-of-pocket expenses ($8,219) are associated with generic glatiramer acetate, both Glatopa and Mylan’s 20 mg/mL and 40 mg/mL generic formulations, approved by the U.S. Food and Drug Administration in 2017. This is more than with any of Copaxone’s formulations. According to the team, this is the result of a higher coinsurance payment (37% vs. 25%) expected for generic medications compared to brand-name options, as well as the fact that manufacturers of generics do not provide discounts toward a beneficiary’s total out-of-pocket spending, unlike what is mandated by the Affordable Care Act for brand-name therapies. “This is a pernicious effect of the release of a generic and an unfortunate effect of Medicare rules,” Dennis Bourdette, MD, one of the study’s co-authors, said. A proposal by U.S. President Donald Trump's administration addresses this by eliminating manufacturer discounts from the calculation to determine a patient’s total out-of-pocket spending. Such strategy would reduce the disparity between brand-name and generic therapies, the researchers said. “In this study we found that Medicare beneficiaries with MS who require a [DMT] face considerable policy-related access restrictions and high out-of-pocket spending,” the researchers wrote. “There is an urgent need for policies that slow the growth of drug prices, improve access, and shield patients from excessively high out-of-pocket spending,” they concluded.

February 5, 2019 News by Patricia Inacio, PhD

Genetic Variants in Inflammasome Genes Influence MS Severity, Progression, Study Suggests

Genetic variants that enhance the activity of the NLRP3 inflammasome or the interleukin-1 beta cytokine are linked to higher severity and progression of multiple sclerosis, a study suggests. Previous studies with mouse models of MS have shown that a complex of innate immune system receptors and sensors, known as the inflammasome, is likely a player promoting the immune system’s attack on the central nervous system in MS and, consequently, the loss of myelin. Follow-up studies showed that people carrying mutations that enhance the function of the NLRP3 inflammasome — one of the three components of the inflammasome complex — had a worse prognosis, once again supporting the role of the inflammasome in MS. Once activated, the inflammasome triggers an enzyme called caspase-1 that promotes the production of two very powerful proinflammatory cytokines called interleukin (IL)-1 beta and IL-18. To further evaluate the role of the inflammasome in MS, a team led by researchers at the Universidade de Sao Paulo in Brazil analyzed the genetic sequence of five inflammasome genes — NLRP1, NLRP3, NLRC4, IL-1 beta, and IL-18 — in blood samples retrieved from 264 patients diagnosed with MS or other demyelinating diseases. They also analyzed 233 healthy individuals used as controls. The team specifically looked at eight variations in certain nucleotides (the building blocks of DNA), called single nucleotide polymorphisms (SNPs). Previous studies reported a link between SNPs in inflammasome-related genes and certain forms of MS. Results showed that SNPs associated with low serum levels of IL-18 were significantly less frequent in MS patients than in controls. In contrast, variants that enhance the function of NLRP3 and IL-1 beta were associated with severity and progression of MS, as measured by the Expanded Disability Status Scale. These results suggest that the "activation of NLRP3 inflammasome could represent a risk factor for MS clinical presentation,” the researchers wrote. A particular variant in the NLRC4 gene was less frequent in patients whose disease progressed rapidly compared with those who had a slower disease, an intriguing observation, according to researchers, suggestive of a “protection effect of this variant against a bad prognosis.” Carriers of this variant also responded better to treatment with interferon-beta. Regarding MS type, the genetic variant that promotes the function of the IL-1 beta gene was significantly more frequent in progressive forms of MS than in relapsing-remitting MS, strengthening once again the negative effects of IL-1 beta in the disease. An analysis of inflammasome activity in blood monocytes, a group of immune cells, showed that the inflammasome is permanently activated in MS compared with healthy controls. "This study emphasizes that a constitutive activation of NLRP3 inflammasome, principally through IL-1 beta production, represents a risk factor for both the development of MS and the progression to severe forms of the disease. On the other hand, low IL-18 production and/or NLRC4 activation were beneficial for MS patients,” the team concluded.

February 1, 2019 News by Alice Melão, MSc

Study Shows Benefits of Low Temperature Exercise for MS Patients

Reducing body temperature during physical exercise can help rewire the brain and improve motor control in patients with multiple sclerosis (MS), a new research study at Canada’s Memorial University shows. Physical exercise can have several benefits for patients with MS, including improved strength and reduced symptoms of fatigue and…

January 29, 2019 News by Patricia Inacio, PhD

Gilenya Better at Lowering Relapse Rate than Tecfidera or Aubagio, Study Suggests

Gilenya is linked to significantly lower annualized relapse rates in relapsing-remitting multiple sclerosis (RRMS) patients compared to Tecfidera or Aubagio, a study suggests. All three therapies showed similar effects on disability outcomes. Oral immunotherapies — including Novartis’ Gilenya, Biogen’s Tecfidera, and Sanofi Genzyme’s Aubagio — are currently standard therapies for RRMS treatment. But while these therapies are highly effective at modulating MS activity, studies comparing their efficacy on relapse and disability are missing. This is an important point for MS patients, so that if a change in oral therapies is needed (due to lack of tolerance, for example), the decision on a more suitable therapy is based on scientific evidence. To address this matter, a group of researchers used the MsBase, an international observational MS cohort study, to identify RRMS patients who had been treated with Gilenya, Tecfidera, or Aubagio for at least three months. The team compared Tecfidera versus Aubagio, Gilenya versus Aubagio, and Gilenya versus Tecfidera, specifically for the therapy’s impact on relapse activity, six-month disability worsening or improvement, and persistence of treatment. Relapse was defined as the occurrence of new symptoms or exacerbation of existing ones for a period of over 24 hours, at least 30 days after a previous relapse. Disability was assessed using the Expanded Disability Status Scale (EDSS); the six-month disability worsening or improvement were defined as an increase or a decrease by one value in EDSS. The study included 614 patients treated with Aubagio, 782 with Tecfidera, and 2,332 with Gilenya. Patients were followed over a median of 2.5 years. Patients’ characteristics at baseline differed among the three groups. Aubagio-treated patients tended to be older, with longer periods of disease, fewer relapses, and lower EDSS scores compared to the other two groups. Patients treated with Gilenya had higher EDSS and more relapses during the prior year, compared to those treated with Tecfidera. The majority of the patients had been treated with other immunotherapies prior to being given one of these three oral treatments. Results showed that Gilenya-treated patients had significantly lower annualized relapse rates than those treated with Tecfidera (0.20 versus 0.26) or Aubagio (0.18 versus 0.24), while patients taking either Tecfidera or Aubagio had a similar rate. However, during the 2.5-year period analyzed, researchers found no differences in disability accumulation or disability improvement among the three therapies. Regarding treatment persistence, Tecfidera and Aubagio were more likely to be discontinued than Gilenya. Overall, the results suggest that treatment with Gilenya may have a greater impact on relapse frequency in RRMS patients compared to Tecfidera and Aubagio, although the "effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment," researchers said. “Choosing a therapy in individual patients remains a complex task that requires thorough and individualized evaluation of disease prognosis, and the corresponding risks and benefits of the increasing number of available therapies,” they concluded.

January 29, 2019 News by Santiago Gisler

Funding Supports MS Research on Epigenetics and Fatigue in Australia

Australian researchers from the University of Newcastle and the Hunter Medical Research Institute (HMRI) have received funding for two projects that will study unexplored areas in multiple sclerosis (MS). The projects, investigating the role of epigenetic differences in MS severity and treatment against MS-derived fatigue, received $211,000 AUD (about $151,300…

January 28, 2019 News by Jonathan Grinstein

Altered Oligodendrocyte Diversity Contributes to Multiple Sclerosis, Study Suggests

Subpopulations of oligodendrocytes — cells that produce the myelin sheath that protects nerve fibers — are altered in patients with multiple sclerosis, a study shows. These findings suggest that oligodendrocyte diversity and the different functions of these subpopulations might have a greater role in the disease than previously thought. The severity of MS varies greatly, and the patient's disability level does not correlate well with the degree of myelin loss. This suggests that other factors contribute to MS severity. One such factor may be that oligodendrocytes are heterogeneous — diverse in makeup and function. For example, oligodendrocytes in mouse spinal cords are known to naturally produce longer myelin sheaths than oligodendrocytes in the mouse brain. Additionally, individual oligodendrocytes have been shown to have different molecular makeups. However, the extent of human oligodendrocyte diversity and its possible contribution to MS pathology remains unknown. Researchers from the Karolinska Institutet and the MRC Centre for Regenerative Medicine studied the differences of individual human oligodendrocytes from healthy and MS brains to assess their diversity. Specifically, the team examined oligodendrocytes from the white matter areas of post-mortem human brains both from MS and non-MS patients. The team examined the RNA content — the messenger molecule carrying instructions from DNA for the production of proteins — from individual oligodendrocytes. Researchers identified groups of RNA molecules that defined features of oligodendrocytes from healthy human white matter. Some of these groups match those that defined oligodendrocytes in healthy mice. Strikingly, some of these RNA molecules in healthy brains were under-represented in oligodendrocytes from MS brains, whereas others were more prevalent. “We found that oligodendrocytes are a diverse population of cells and that different types are likely to have different functions in the brain,” Charles ffrench-Constant, the study's co-lead author, said in a Karolinska Institutet news release written by Katarina Sternudd. These differences in oligodendrocyte RNA content may indicate different functional states of oligodendrocytes in MS lesions. “The proportions of different resident oligodendrocytes in the lesions are changed, along with their properties, suggesting that they might have important roles in MS,” said Eneritz Agirre, PhD, a study co-author. Furthermore, the researchers believe that this altered diversity in oligodendrocytes in MS may be important to understand disease progression and develop therapeutic approaches. “Understanding which types of oligodendrocytes are most beneficial in repairing myelin will be crucial for maximizing the chances of developing much-needed treatments for MS,” said Anna Williams, PhD, study co-lead author. The team concluded that the changes in different oligodendrocyte subpopulations in MS suggest "a more complex role of these cells in the pathology of the disease, but also in regeneration of new cells,” said Gonçalo Castelo-Branco, PhD, another study co-lead author.

January 24, 2019 News by Patricia Inacio, PhD

Study of Myelin Debris Sheds Light on Brain Inflammation in MS

Endothelial cells, those lining the inside of small blood vessels, promote clearance of myelin debris — a common detrimental outcome of demyelinating diseases such as multiple sclerosis (MS) or spinal cord injury. However, in its path to clear the brain from myelin debris, endothelial cells trigger more damaging mechanisms, promoting…

January 24, 2019 News by Jonathan Grinstein

New Products Intended to Stimulate Feet of MS Patients

Naboso Technology has expanded its product offerings with new insoles and training mats specifically designed to stimulate the nervous system through the skin on the bottom of the feet. The products were developed to help improve balance, posture, movement and restore motor function, as part of a neurorehabilitation strategy…

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