Multiple Sclerosis News Today brought you daily coverage of the latest scientific findings, treatment developments, and clinical trials related to multiple sclerosis (MS) throughout 2020, a year marked by the COVID-19 pandemic.
We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2021.
Here are the top 10 most-read articles of 2020, with a brief description of what made them relevant for the MS community.
Results from a small clinical trial (NCT03032601) showed that two months of treatment with N-acetylcysteine, or NAC — a natural and powerful antioxidant — significantly improved brain metabolism, cognitive function, and attention in people with MS. Sold as an oral dietary supplement and as an intravenous medication to prevent liver injury due to oxidative stress, NAC has direct and indirect antioxidant properties, including the increase of an antioxidant molecule found in neurons called glutathione. Oxidative stress, a known driver of the underlying processes of MS, is an imbalance between the natural production of potentially harmful reactive oxygen species and the ability of cells to detoxify them with antioxidant agents. Larger studies are needed to confirm NAC’s clinical benefits in this patient population.
A study in mice suggested that boosting a natural process that mobilizes mitochondria — organelles that provide energy to cells — to the sites where myelin, the protective sheath that surrounds nerve fibers, is being lost, may help prevent neurodegeneration. Myelin loss is a hallmark of MS, and mitochondria function, namely the complex IV (a key component for energy production), is deficient in progressive MS. In the study, treating complex IV-deficient mice with pioglitazone, a type 2 diabetes medicine that promotes mitochondria production, increased mitochondria transport inside neurons to the sites of myelin damage, providing them the needed energy. This protected the cells from further damage and neurodegeneration, suggesting that boosting this natural response to myelin damage may be a potential neuroprotective approach for MS.
Researchers in Italy described the case of a 48-year-old man with relapsing-remitting MS (RRMS) who lost vaccine-based immunity against the varicella-zoster virus — which causes chickenpox and shingles — after the first dose of Ocrevus (ocrelizumab). An antibody-based therapy approved for people with relapsing MS and primary progressive MS, Ocrevus works by blocking the activity of mature B-cells, a type of immune cell involved in the immune attacks against myelin seen in MS. While the therapy was previously shown to preserve immunity acquired from previous infections or vaccinations, there have been some reports of loss of vaccine-based immunity against certain viruses and bacteria after Ocrevus treatment. Based on the current case, the authors recommended that MS patients treated with Ocrevus be retested for immunity against the varicella-zoster virus.
Preliminary data from 232 MS patients in Italy who tested positive or were suspected to have a COVID-19 infection as of April suggested that most people with MS were likely to have a mild infection, similar to the general population. The results, based on information collected through an international web platform — called MuSC-19 and donated by Roche — also suggested that disease-modifying therapies (DMTs) use may not raise MS patients’ risk of a severe infection. Notably, a more recent study based on the largest data currently available worldwide regarding MS and COVID-19 showed that the use of two DMTs targeting B-cells — Ocrevus and rituximab (used off-label in MS) — was associated with a more severe infection but not death.
Researchers in Canada found that people living close to major roads or highways have a higher risk of developing neurological conditions, including MS. The study, based on data from 678,000 people, ages 45–84, in metropolitan Vancouver, evaluated whether exposure to environmental factors such as road proximity, air pollution, greenness, and noise affected the risk of MS, Parkinson’s disease, Alzheimer’s disease, and non-Alzheimer’s dementia. The data also showed that living near green spaces in urban areas that might lower exposure to air pollutants lessened the likelihood of developing some of these neurological diseases, but not MS. The lack of such beneficial effect in MS may be due to intrinsic limitations of the statistical model used, the researchers noted.
In late March, the U.S. Food and Drug Administration approved Bristol Myers Squibb’s oral therapy Zeposia (ozanimod) for adults with relapsing forms of MS, including RRMS, active secondary progressive MS (SPMS), and clinically isolated syndrome. With this approval, Zeposia became the first sphingosine-1-phosphate (S1P) receptor modulator approved for MS that doesn’t require patients to undergo a genetic test or a first-dose observation period. This type of therapy works by “trapping” immune cells in lymph nodes (immunological structures), potentially limiting their damaging, pro-inflammatory effects in the brain and spinal cord. The decision was based on data from two global Phase 3 trials — SUNBEAM (NCT02294058) and RADIANCE part B (NCT02047734). Results showed that Zeposia was superior to Biogen’s Avonex (an injectable formulation of interferon beta-1a) at lowering the number of relapses and brain lesions, preventing brain shrinkage, and improving cognitive processing speed in people with RRMS or active SPMS. Notably, these findings also supported Zeposia’s approval in Europe for RRMS patients two months later.
Researchers in the U.S. found that 0.62% of nearly 320,000 people originally diagnosed with MS were later diagnosed with neuromyelitis optica spectrum disorder (NMOSD). NMOSD is a neurological inflammatory disease that also affects the brain and spinal cord, with symptoms that are similar to MS. Further analyses also showed that four (7.4%) of the 54 MS patients followed at the University of Kentucky Medical Center actually had NMOSD. Based on these findings, the researchers advise that NMOSD-specific tests become mandatory, rather than recommended, in MS diagnostic guidelines. Ruling out NMOSD is particularly important since medications frequently used to treat MS may worsen NMOSD, they noted.
A review study found that specific variations in the vitamin D receptor (VDR) are associated with an increased risk of developing MS. Vitamin D modulates the immune system by binding to its receptor, and therefore changes in VDR’s amino acid sequence — the building blocks of proteins — may affect how this vitamin works and is metabolized in the body. These findings suggest that specific mutations in this receptor may increase the risk of MS. They also support the large body of evidence suggesting that vitamin D is an important immunomodulator in MS, and its deficiency or impaired function may increase the risk of the disease or of relapse and earlier disability.
An international team of researchers found that while long-term supplementation with a moderate dose of vitamin D can ease disease severity in a mouse model of MS, a high dose may “lead to much worse disease,” Sebastian Torke, PhD, the study’s first author, said in a poster presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020 in February. The data showed that high-dose supplementation increased calcium levels throughout the body, which promoted the activation and growth of pro-inflammatory immune T-cells and increased their ability to infiltrate the central nervous system (CNS; the brain and spinal cord). These effects were associated with massive CNS inflammation and with myelin loss. “Our data caution that in light of the currently limited information on a direct beneficial effect of vitamin D in MS, MS patients may be at danger of experiencing untoward immunological and/or clinical effects when vitamin D is supplemented excessively,” Torke concluded.
Our most-read article of 2020 concerned the discovery that vitamin D supplements promote a shift toward an anti-inflammatory state in people with MS by raising the levels of two molecules called IL-27 and TGF-beta 1. While previous research had shown that taking these supplements was linked to higher levels of anti-inflammatory molecules and lower levels of pro-inflammatory molecules in MS patients, this study unraveled the key drivers of these molecular changes. Data showed that vitamin D supplements significantly boosted the production of both IL-27 and TGF-beta 1 in MS patients, their first-degree relatives, and healthy, unrelated individuals, but this increase was greater in MS patients. Notably, similar, but less pronounced, IL-27 and TGF-beta 1-associated anti-inflammatory effects were also observed in MS patients’ relatives, suggesting that vitamin D supplements may be used as a preventive approach for MS. Further studies are required to confirm these findings and to clarify the clinical benefits of these vitamin D-induced molecular changes in MS patients, the researchers noted.
At Multiple Sclerosis News Today, we hope these stories and our reporting throughout 2021 contribute to informing and improving the lives of everyone affected by MS.
We wish all our readers a happy 2021.
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