disease progression

Cellular senescence — the process of aging at the cellular level — may play a role in the development of primary progressive multiple sclerosis (PPMS) by limiting the ability of myelin-producing cells (oligodendrocytes) to renew and mature. The study with that finding, “Cellular senescence in progenitor…

A new web portal called Talk2Me that detects early changes in language could help doctors diagnose or determine progression in neurodegenerative disorders like multiple sclerosis (MS), the scientists who created it suggest. The open platform portal, which gathers language data through an array of cognitive tasks performed…

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."

T20K, Cyxone‘s lead compound for treating multiple sclerosis (MS), seems able to prevent or slow disease progression, according to data from preclinical studies. Based on these findings, the company is confident that T20K might become a prophylactic (preventive) medication for MS in the near future. T20K is a…

Two-year treatment with temelimab reduced brain atrophy, or shrinkage, preserved myelin, and reduced disease progression in patients with relapsing-remitting multiple sclerosis (RRMS), according to findings from an extension study of a Phase 2b clinical trial. Temelimab, previously known as GNbAC1, is a monoclonal antibody that neutralizes the MS-associated human…

The evaluation of disease progression in multiple sclerosis (MS) patients through magnetic resonance imaging (MRI) can be performed without the use of a contrast agent, new research has shown. These findings suggest that routine use of contrast-enhanced MRI is unnecessary for most follow-ups with MS patients, reducing both imaging…

MSCopilot, a software device designed for the self-assessment of multiple sclerosis (MS), distinguishes between patients and healthy controls, and potentially could be used in clinical practice for the monitoring of MS disability progression and patients’ response to treatment. Matthieu Lamy, from Ad Scientiam, the…

The rate of spinal cord tissue loss is a strong indicator of conversion from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS), according to a finding presented at the fourth annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019. The forum…

The RhoE protein has been identified as being important for axons’  myelination and extension in the central nervous system, two processes that go awry in diseases like multiple sclerosis (MS). The findings stem from Pilar Madrigal’s doctoral thesis, “Role of the small GTPase RhoE in myelination and axonal tracts development.”…

Life never lets me forget its fragility. Sometimes my challenges seem like mountains to be scaled. Adversity has become the elephant in the room; it is ever present even when I refuse to acknowledge it. A few weeks ago, I faced what could potentially have been a medical crisis.

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.

“If I were you two, I think I’d plan for the worst,” Amy, my physiatrist, said to my wife and me as we sat in the examination room. It was just after 11 a.m. on Friday, Jan. 18. January has become one of two pivotal months in terms of…

Fatigue is more prevalent among patients with progressive multiple sclerosis (MS), according to a study that surveyed patients on fatigue and factors related to it. In addition, increased fatigue severity correlated with greater physical, cognitive, and psychological impairment, although the strength of this link was largely the same…

Autologous hematopoietic stem cell transplant is better than disease-modifying therapies (DMT) at reducing the risk of disease progression in patients with relapsing-remitting multiple sclerosis (RRMS), results from the MIST clinical trial show. The study “Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression…