MS lesions

Investigational therapy evobrutinib, also known as M2951, can reduce relapse rates and brain lesions in people with relapsing forms of multiple sclerosis (MS), 48-week data from a Phase 2 clinical trial suggest. Updated results from the trial (NCT02975349) were presented at the recent 2019 annual…

Lyfebulb and Celgene have announced the 10 finalists who will compete for a $25,000 grant to support the development of their innovative proposals that address an unmet need in multiple sclerosis (MS).  The Lyfebulb-Celgene 2019 “Addressing Unmet Needs in MS: An Innovation Challenge,” will take…

Quanterix is leading the research presented at this year’s American Academy of Neurology (AAN) Annual Meeting, validating the use of neurofilament light chain (NfL) as a potential biomarker for the diagnosis, prognosis, and treatment monitoring of patients with multiple sclerosis (MS) and other neurodegenerative diseases. The company…

Treatment with Tysabri (natalizumab) lowers the levels of the biomarker serum neurofilament light chain (sNfL) in patients with secondary progressive multiple sclerosis (SPMS), according to data from a Phase 3 trial. Findings also revealed that higher levels of sNfL correlated with MS lesions and disease activity prior to starting the…

Giving estrogen to two different adult mouse models of multiple sclerosis (MS), including the experimental autoimmune encephalomyelitis (EAE) model, promoted remyelination, a new study shows. Exposure to the hormone affected gene activity in oligodendrocytes, tricking them into producing myelin (the fatty substance that protects nerve cells, and that is destroyed…

People who cover medical issues often write about mouse studies. These stories can regularly be found on traditional news outlets, both broadcast and print, as well as online platforms. That includes the website on which you’re reading this column. I’m one of the mouse study writers, though I try to…

The National Multiple Sclerosis Society has recently awarded $24.4 million in grants to support 64 research projects on multiple sclerosis (MS) worldwide, including $750,000 to fund 14 high-risk, high-reward pilot projects that will test new ideas and seek answers to new and relevant questions. According to a society…

Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about MS? Visit our forum. This week’s question is inspired by the forum topic “Gadolinium – The contrast agent used in MRI scans,” from April 10,…

Oligodendrocyte precursor cells (OPCs), the cells responsible for myelin production, are unable to migrate into sites of myelin loss in the brain. These cells then cluster and disrupt the blood-brain barrier (BBB), triggering an inflammatory process in the early stages of multiple sclerosis (MS), a study shows. The study, “Aberrant oligodendroglial–vascular interactions disrupt the blood–brain barrier, triggering CNS inflammation,” was published in the journal Nature Neuroscience. MS is an autoimmune disease characterized by the loss of myelin (demyelination) — the fat-rich substance that protects nerve fibers — which leads to neurodegeneration. Along with loss of myelin, researchers have observed that the blood-brain barrier — a highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation — breaks down in the initial stages of disease. A team led by researchers at the University of California, San Francisco, have now discovered that OPCs are involved in the disruption of the blood-brain barrier in MS, according to a press release from the National MS Society, which funded the study. Oligodendrocytes are myelin-producing cells and are responsible for myelinating the nerve cells’ axons — a single oligodendrocyte is capable of myelinating multiple axons. Mature myelin-producing oligodendrocytes develop from more immature, stem cell-like OPCs. In a normal brain, upon myelin loss, OPCs are called into action and travel into the damage site where they mature and generate myelin-producing oligodendrocytes. In this study, the researchers found that OPCs in MS form clusters in blood vessels of the brain-blood barrier, having lost the ability to detach from these vessels and migrate to injury sites. In an animal model of MS, they saw that OPC aggregates altered the location of other cells — called astrocytes — in a competition for space, and contributed to the disruption of blood vessels. Astrocytes are a group of star-shaped cells, belonging to the group of glial cells, that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation. The team also observed that OPC aggregates trigger an immune inflammatory response, shown by a large number of microglia (the central nervous system immune cells) and immune cells called macrophages around these cell clusters. “We find in several MS cases, in lesion areas with active inflammation, that OPCs can be found clustered on vasculature, representing a defect in single cell perivascular migration and inability to detach from blood vessels,” the researchers wrote. Further molecular analysis revealed that OPCs have high levels of Wnt signaling, and elevated secretion of Wif1 factor to the extracellular space that could explain why OPCs accumulate and destroy the blood-brain barrier. The WiF1 factor is actually a negative regulator of Wnt signaling that is essential for the maintenance of the blood-brain barrier structure. This factor competes with Wnt ligands, and affects the integrity of cellular junctions, making the blood-brain barrier more fragile and permeable. "Evidence for this defective oligodendroglial–vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB,” the researchers wrote. They suggested that more studies are needed to better understand the interactions between blood vessels and oligodendrocytes, which could help identify new therapeutic targets for promoting myelin repair in MS.

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…

This year’s John Dystel Prize for Multiple Sclerosis Research is being awarded to Anne H. Cross, a neurologist and MS chair in the department of neuroimmunology at  Washington University School of Medicine in St. Louis, for her research into the role of immune B-cells in multiple sclerosis attacks and new imaging…

A protein that promotes nervous system repair through remyelination — the creation of myelin, the protective sheath around nerve cells — in mice also is found in remyelinating plaques in brains of multiple sclerosis (MS) patients, new research shows. This protein potentially represents a new therapeutic target in demyelinating…

Rituximab-treated multiple sclerosis (MS) patients who take vitamin D supplements have less inflammatory activity, a study reports. Increased levels of vitamin D were associated with beneficial treatment outcomes, such as better self-perceived health and reduced levels of the inflammation marker C-reactive protein…

High blood levels of a signaling protein known as TWEAK are associated with active neuroinflammation in patients with multiple sclerosis (MS), a study shows. This finding suggests that TWEAK may be a valuable biomarker to assess ongoing inflammation and overall MS activity, and potentially help optimize patient care. The…

A shortened DNA molecule showed an increased ability to bind myelin in human cells, and may boost the development of remyelination approaches for multiple sclerosis (MS) treatment, according to a study. The study, “Optimization of a 40-mer Antimyelin DNA Aptamer Identifies a 20-mer with Enhanced Properties…

Schwann cells surrounding neurons protect the degeneration of nerves by blocking thrombin, a blood-clotting protein that can also damage nerves, according to a new study. These findings may aid in the further understanding of genetic and molecular mechanisms behind conditions such as multiple sclerosis (MS). Results of the study, “Glial cells…

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…

In the time necessary to perform a standard multiple sclerosis (MS) functional exam, gamified tests on a smartphone app provide much richer and reliable measurements of several distinct neurological functions, according to new data. These findings suggest that creatively-constructed smartphone apps may one day recreate entire neurological exams.

Full results of a Phase 2 clinical trial testing TG Therapeutics’ lead candidate ublituximab (TG-1101) for relapsing multiple sclerosis (MS) showed that treatment for 48 weeks resulted in a marked reduction of brain and spinal cord lesions, an almost complete depletion of relapse-associated immune B-cells, and significantly halted disability…

The levels of epsilon toxin are increased in multiple sclerosis (MS) patients, and its presence in laboratory rodents replicated some aspects of disease activity, according to data presented at the 4th Annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum. The researchers suggested that the epsilon…

My memory is spotty at times. I utter phrases like, “What was I looking for?” more often than I care to admit. I attribute my memory lapses to my multiple sclerosis (MS) brain lesions. But is my assumption accurate? What if it is age-related or…

A method based on cerebrospinal fluid measurements and magnetic resonance imaging (MRI) can aid in stratifying patients with multiple sclerosis (MS) at the time of diagnosis, which may help identify a tailored therapeutic approach for each patient from early disease stages. The data was presented by Roberta Magliozzi, from…

Evobrutinib, Merck KGaA’s oral candidate for relapsing multiple sclerosis (MS), is safe and can significantly reduce active brain lesions over 24 weeks of treatment, results of ongoing Phase 2 study show. Xavier Montalban, PhD, MD, with Vall d’Hebron University Hospital in Barcelona, presented the results in the talk “Primary…

As the protective molecular caps of our genetic information — called telomeres — become shorter in certain immune cells, the extent of multiple sclerosis (MS) disability progression increases, regardless of age, researchers at the University of California, San Francisco (UCSF) reported. The findings were presented at the annual…

Kessler Foundation researchers Ekaterina Dobryakova, PhD, and Pei-Pei Liu, PhD, have been awarded a $50,000 grant by the National Multiple Sclerosis (MS) Society to study the speed at which MS patients process information during social interactions. A better understanding of how MS affects the way a person learns from others’…

Podocalyxin, a protein found in cells lining the interior of blood vessels, is key for maintaining the integrity of the blood-brain barrier (BBB) in mice with systemic infection, suggesting its potential as a therapeutic target for neurodegenerative diseases such as multiple sclerosis (MS), a study shows. Disruption of the…

Two newly identified variants of the known pharmaceutical agent chloroindazole showed significant anti-inflammatory and neuroprotective benefits in a mouse model of multiple sclerosis, a new study shows. Multiple sclerosis is an autoimmune, demyelinating disease of the central nervous system with no known cause or cure. Patients with MS characteristically show loss of the myelin sheath, a protective coat in nerve cells that helps increase cell-to-cell signaling. Several studies have suggested that estrogens — a type of hormone — are beneficial to the functioning of the central nervous system, and help regulate the immune system. Thus, they are attractive candidates for the treatment of MS. However, despite their potential to treat MS, estrogen-based therapies can have several undesirable side effects, such as feminizing male recipients and increasing the risk of developing breast and endometrial cancers in females. Interestingly, estrogens work by binding and activating two different types of receptors: the estrogen receptor (ER)α and ERβ. The cancer-inducing effects of estrogens are mediated mainly through estrogen receptor ERα. Hence, therapies that specifically target ERβ can bypass these deleterious effects. Chloroindazole (IndCl), a pharmaceutical agent, has up to 100-fold relative binding affinity for ERβ over ERα. IndCl has been shown previously to have beneficial effects on modulating the immune system and the central nervous system, and inducing myelination of nerve cells in mouse models of MS. Furthermore, IndCl and other ERβ-activating agents directly support the growth, differentiation (maturation), and overall myelination activity of oligodendrocytes, which are the nerve cells that produce the myelin sheath. Therefore, in order to optimize the benefits of IndCl, researchers developed and screened seven novel IndCl analogues for their ability to promote oligodendrocyte survival, growth, and differentiation. These analogues have a molecular structure closely similar to that of IndCl, but interact with estrogen receptors in subtly different ways. Among these seven compounds, researchers found two analogues — IndCl-o-chloro and IndCl-o-methyl — that stimulated growth and differentiation similar to the original IndCl. Next, researchers evaluated the benefits of these compounds in a mouse model of MS — the experimental autoimmune encephalomyelitis (EAE) mouse model — to determine whether they could alter the disease course, white matter pathology (level of demyelination), and inflammation. Results indicated that both compounds “ameliorated disease severity, increased mature OLs [oligodendrocytes], and improved overall myelination in the corpus callosum and white matter tracts of the spinal cord,” researchers wrote. Corpus callosum is a thick band of nerves that connect the left and right side of the brain. White matter tracts connect the cortex (the largest part of the brain) with other areas in the central nervous system. These beneficial effects were accompanied by a reduced production of the toxic, inflammatory molecules interferon-γ and CXCL10. Additionally, IndCl-o-methyl also reduced the levels of peripheral interleukin (IL)-17, a molecule that strongly induces inflammation. Furthermore, IndCl and both analogues upregulated the expression of a compound called CXCL1, which is associated with increased production of oligodendrocytes. Not only were these two newly identified compounds equivalent to IndCl, but the two analogues performed better in reducing disability and encouraging remyelination than the original compound, and without any obvious side effects. “The o-Methyl and o-Chloro IndCl analogues represent a class of ERβ ligands that offer significant remyelination and neuroprotection, as well as modulation of the immune system; hence, they appear appropriate to consider further for therapeutic development in multiple sclerosis and other demyelinating diseases,” the researchers concluded. “We believe we created a drug that does two things really well, modulating inflammation and allowing axon remyelination. No other drug on the market can do these two things simultaneously,” Seema K. Tiwari-Woodruff, said in a press release written by Stacy Kish. Tiwari-Woodruff is the study's lead author. “The most amazing part of the study is that these new analogues of a known estrogen modulator, chloroindazole, are superior in treating mouse model of multiple sclerosis,” she added. The team has patented the analogues, and hopes to begin further pharmacological and toxicity studies soon.

A protein called Satb1 appears to be the "on switch" that turns a type of T-cell called Th17 from its typical protective role into one that is disease-causing, and key in the development of multiple sclerosis (MS) and other inflammatory autoimmune disorders, a study reports. These findings suggest that Satb1 may be a therapeutic target for autoimmune diseases like MS. The research article, “Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation,” was published in the journal Nature Communications. Immune cells called T-helper 17 (Th17) cells play a range of roles in immunity, including protecting against infecting pathogens — bacteria, viruses, and other microorganisms that can cause disease. But Th17 cells are also players in the development of such autoimmune diseases as MS, psoriasis, inflammatory bowel disease, and rheumatoid arthritis. This is because Th17 cells can be stimulated to become T-cells that engage in pathogenic, or disease-causing, immune programs. How Th17 cells switch from their typical and helpful immunity role to that of a pathogenic actor has not been resolved, although it is thought critical to treating inflammatory autoimmune diseases. An international team led by researchers at Osaka University and Kyoto University, in Japan, tried to identify the mechanism behind the disease-causing program of Th17 cells. To do so, they built upon previous findings showing that a protein regulator called Satb1 is important in the development of Th17 cell subsets. "We have known for some time that Satb1 is indispensable for the development of T-cells in the thymus. However, how it is involved in the regulation of pathogenic processes of Th17 cells in inflamed tissues had not been examined," Keiko Yasuda, MD, the study's lead author, said in a press release. Researchers used a standard mouse model of MS, called experimental autoimmune encephalomyelitis (EAE) mice. These animals had genetically-modified Th17 cells that lacked Satb1. Researchers tested how Th17 cells lacking Satb1 acted when subject to inflammatory conditions, and how they were stimulated to activate a "pathogenic effector program." Interestingly, these modified mice were resistant to the development of EAE, or MS-like, disease. Researchers saw fewer Th17 cells infiltrating the animals' spinal cord. Also, Th17 cells lacking Satb1 showed poorer production of key pathogenic signaling molecules in autoimmunity, notably one called granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is known to cause localized tissue inflammation in MS and other inflammatory autoimmune diseases. Researchers went on to show that Satb1 can act as a switch between benign and pathogenic Th17 cells, depending on their exposure to healthy or inflammatory conditions. They found molecules that boost the pathogenicity of Th17 cells, such as Bhlhe40, and molecules that promote normal immune function, such as PD-1.  Of note, PD-1 is shut down when Th17 cells engage in their pathogenic effector program. These results showed Satb1 to be a key regulator of Th17 cell pathogenicity in these MS mice. Halting Th17 cells from making Satb1 may offer a way of treatting various autoimmune diseases. “Together, our findings, in addition to providing novel insights into the molecular mechanisms underlying the pathogenic program of tissue Th17 cells in mice, may help design novel immunotherapeutic approaches such as small molecule modifiers of Satb1 for the treatment of autoimmune diseases,” the researchers wrote. Future studies are needed to confirm these results in people. A previous study in people also suggested a link between Satb1 and the pathogenic function of Th17 cells in the central nervous system of MS patients. Overall, "our results suggest that manipulating Satb1 gene expression in Th17 cells could form the basis of novel treatments for various autoimmune diseases caused by Th17 cells. If we can prevent the pathogenic processes of Th17 cells, we may be able to alleviate or even eliminate disease symptoms," concluded Shimon Sakaguchi, PhD, one of the study's senior authors.

Almost one in five patients diagnosed with multiple sclerosis (MS) and referred to one of two MS-specialized centers in the U.S. were found to not have the disease, a study at those two centers reported. Migraine was the most common correct diagnosis eventually given these people. The retrospective study…