genetics

DELIVER-MS Trial Recruiting RRMS Patients to Help Improve Treatment Decision-making What’s the best way to attack multiple sclerosis when it’s first diagnosed? Do you hit it hard and fast using the most effective disease-modifying therapy (DMT), or do you start with a lower efficacy DMT and slowly ramp up?…

Scientists are zeroing in on mutations in a few genes that appear to be major risk factors for developing multiple sclerosis (MS). The results of their research suggest there are common biological pathways that cause the disease. The study, “Exome sequencing in multiple sclerosis families identifies 12…

A study found no genetic risk factors associated with vitamin D in families with a history of multiple sclerosis (MS), suggesting that the link between vitamin D deficiency and MS risk is determined by environmental factors rather than a genetic predisposition. The study “Exonic variants of genes related…

A collaboration between DNAnexus, the Sutter Health network, and the University Pittsburgh Medical Center (UPMC) aims to improve personalized medicine in multiple sclerosis (MS) through the first large-scale clinical genomic research study, the companies announced. The network has the goal of improving screening, diagnosis, and treatment of…

A tiny molecule known as microRNA-142 plays a key role in the prevention of autoimmune responses through immune cells called regulatory T-cells (Tregs), according to a new study of  mice. These findings could enable new strategies to treat multiple sclerosis (MS) and other autoimmune diseases, the scientists said. The…

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.

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…

A genetic variant associated with an increased risk of multiple sclerosis (MS) due to its impact on certain immune system cells can also affect brain cells called astrocytes, a study shows. Reported in the study, “Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple…

Risk factors often associated with multiple sclerosis (MS), such as genetic background, obesity and smoking, contribute independently to the disease’s variability and may be an early influence on progression, a study reported. The retrospective study, “Multiple sclerosis risk factors contribute to onset heterogeneity,” was published in the journal …

An international consortium studying more than 68,000 people, about half of them multiple sclerosis (MS) patients, found rare genetic variations that account for up to 5 percent of the heritable MS risk, a study reports. The newly discovered mutations were associated with either an increased…

Lower Fatigue Reported by MS Patients After aHSCT in Canadian Study Fatigue affects 90 percent of people with MS. It certainly impacts my life. This study, though very small, reports a 36 percent reduction in the median modified Fatigue Impact Scale (mFIS) score three years after autologous…

Genetic variants in the CPXM2, IGSF9B, and NLRP9 genes were found to potentially shape the disease course of multiple sclerosis (MS), and may be used as biomarkers to identify those with an aggressive or…

Gender differences are evident in immune system cells of the brain called microglia, a study in male and female mice reports, suggesting these cells’ sex-specific features may be important to treating people with  multiple sclerosis (MS) and other neurological diseases. The study “…

Cerebrospinal fluid of progressive multiple sclerosis (MS) patients may carry lower levels of cell-free mitochondrial DNA, according to a team of researchers who say this may be a sign of neurodegeneration among these patients. The study “Cell-free mitochondrial DNA in progressive multiple sclerosis” was published in the journal Mitochondrion.

Researchers have created a detailed map of the mouse nervous system, including the location of the many diverse cell types in the brain, in the largest study yet of the makeup of the mammalian nervous system.  The new map could provide new clues about the origin of neurological…

Vitamin D3 insufficiency increases multiple sclerosis (MS) susceptibility in a gene and sex-dependent manner, a mouse study suggests. The study with that finding, “Sex-Specific Gene-by-Vitamin D Interactions Regulate Susceptibility to Central Nervous System Autoimmunity,” by researchers at the University of Vermont, was published in the journal Frontiers in…

A genetic variant close to a gene called interferon regulatory factor 6 (IRF6) may help to predict those multiple sclerosis (MS) patients most at risk of liver injury while using interferon-beta therapies, a study reports. The study, “Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis” was published…

Exposure to organic solvents like such as paint or varnish greatly raises the risk of multiple sclerosis (MS), particularly in people who smoke or have a genetic susceptibility to the disease, a large-scale Swedish study reports. In fact, solvent exposure — linked to occupation, like being a painter or working…

Researchers Discover How Key Genetic Risk Factor for MS Operates A genetic link to MS is something that some scientists have suspected for years. Now, there’s new research that targets a variation of a specific gene as possibly being that link. Scientists have uncovered the molecular mechanism…

Scientists have uncovered the molecular mechanism by which the genetic variant HLA-DRB1*15:01 is the strongest risk factor for multiple sclerosis, new research shows. Analyzing several studies, researchers found that the risk linked…

Genetically modified human umbilical cord blood cells can help nerve cells recover the myelin layer necessary for normal functioning, researchers found in a preclinical study. This finding may support the development of cell-based therapeutic approaches to help patients with spinal cord injuries or demyelinating diseases, such as multiple sclerosis (MS).

The Accelerated Cure Project for Multiple Sclerosis and a Regeneron unit are teaming up to sequence the coding portion of genes in DNA samples of multiple sclerosis and other patients in the project’s repository. The cure project is a non-profit organization whose goal is to accelerate research to improve MS diagnosis and…

The idea that a vitamin D deficiency contributes to the risk of developing multiple sclerosis (MS) has been challenged in a recent study that examined subtle differences in a protein involved in vitamin D metabolism in people from different ethnic backgrounds. The study, “Vitamin D-Binding Protein…

A molecule triggered by the male hormone testosterone protects male mice from developing multiple sclerosis, Northwestern Medicine researchers report. Their discovery may help explain why MS affects more women than men. It could also lead to targeted therapies to protect women against the disease. The study, “…

Researchers have found a link between variations in two genes that control our 24-hour biological clock and the risk of a person developing multiple sclerosis. The study, “Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis,” was published in the journal PLOS ONE. Scientists know MS…

Smoking changes a DNA-based mechanism that influences multiple sclerosis patients’ gene activity, a Swedish study confirms. Another finding was that MS appears to aggravate the harmful effects of smoking. The study dealt with DNA methylation, the process by which the body adds methyl groups to a DNA molecule. Methylation can change…

Researchers have taken the first steps towards the development of a gene therapy for multiple sclerosis — a treatment that boosted anti-inflammatory immune processes and reversed severe paralysis in mouse models of the disease. The University of Florida Health research team said it was optimistic that the therapy can work…

University of Southern California researchers are recruiting 400 Hispanics who have been diagnosed with multiple sclerosis in the past two years for a study about genetics’ and cultural perceptions’ effect on the severity of the disease. More specifically, the Keck School of Medicine team will look at whether the stressful process of…

For the first time, scientists have shown they can correct gene mutations in human embryos — a breakthrough with implications for multiple sclerosis (MS) and several other diseases. This landmark study was a collaboration involving scientists at the Salk Institute in La Jolla, California; the Oregon Health & Science University in…

(Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with the second of two columns about terms starting with the letter “G.” Read more “G” terms here.) Mastering an understanding of multiple sclerosis means you need to mind your Ps…