The complexity in underlying mechanisms, a lack of representative research models, and inconsistent criteria defining therapeutic benefit are the main reasons why an effective therapy for progressive forms of multiple sclerosis (MS) is still lacking, researchers maintain in a review study. Nevertheless, as research continues to shed light on…

Interleukin-17A (IL-17A), a molecule that mediates immune and inflammatory responses, likely promotes inflammation and tissue damage in relapsing-remitting multiple sclerosis (RRMS) and should be considered a potential target for treating the disease, a study reports. The findings of the study, “IL-17A is associated with the breakdown of the…

Obesity, altered lipid (fat) levels, and elevated leptin — an hormone produced by fat cells — may contribute to neuroinflammation, and worse disease severity in people with relapsing-remitting multiple sclerosis (RRMS), research has found. A study with the findings, titled “Obesity worsens central inflammation and disability in multiple…

The pro-inflammatory protein interleukin-17 (IL-17) drives inflammation by promoting a chemical modification, called phosphorylation, in the RNA molecule of the regnase-1 enzyme, a mouse study shows. These findings support the development of therapeutics that block the phosphorylation of regnase-1 to halt IL-17-mediated inflammation, as seen in multiple…

Reactivation of ancient viruses incorporated into the human genome in the course of evolution may be involved in the acute inflammatory response that is characteristic of multiple sclerosis (MS), a study says. The findings of the study, “Expression of endogenous retroviruses reflects increased usage of atypical enhancers in…

Treatment with Mayzent (siponomod) may reduce myelin deterioration by lessening the accumulation of immune cells in brain meninges, and preventing the migration of pro-inflammatory lymphocytes into the brain, according to a study in a mouse model of multiple sclerosis (MS). The research, “A Mouse Model of…

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…

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…

Increased production of an anti-inflammatory molecule called interleukin (IL)-10, and suppression of a subtype of immune T-cells, may mean that a fatty acid called pentanoate is effective against inflammatory and autoimmune diseases such as multiple sclerosis (MS), according to new research in mice. The study, “The…

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…

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.

Previously unknown immune cell subtypes are present in the inflamed brain of mice models of multiple sclerosis (MS), a new study reports. According to the researchers, these subsets of myeloid cells (cells derived from hematopoietic stem cells in the bone marrow) can offer a strong basis for therapeutic targets in neuroinflammatory and…

Tiny ruptures in the cell membrane of nerve fibers enable the entry of calcium and ultimately lead to their degeneration, a study in a mouse model of multiple sclerosis (MS) suggests. The study, “Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple…

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…

The herbicide linuron, commonly used with other herbicides, insecticides and fungicides to control the growth of grass and weeds, may be an important environmental risk factor in the development of neurological diseases that include multiple sclerosis, researchers suggest. Used in the U.S. and other countries — but recently…

Blood infection with the yeast Candida albicans, a type of fungus, can reach the brain and trigger an immune response, a new mouse study shows. Although the fungus can be cleared within 10 days, it affects the spatial memory of mice. These findings are the first evidence that a blood infection with a…

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 was inspired by the forum topic “Do you know any natural remedies that help fight inflammation?“, from May…

An altered metabolism and signaling is associated with the ability of a subset of immune T helper 17 (Th17) cells to induce neuroinflammation, according to a new study of mice. The findings may lead to new treatments for multiple sclerosis (MS) and other chronic inflammatory diseases, the scientists said.

Unusually high levels of a transcription factor called paired related homeobox protein 1 (PRRX1) in human oligodendrocyte progenitor cells hinders their ability to respond to the loss of myelin and to transform into mature, myelin-producing oligodendrocytes, a new study shows. These findings suggest a new potential way of treating …

Multiple sclerosis (MS) patients who reported food allergies showed a 27 percent higher cumulative rate of flare-ups over the course of their disease, and more than twice the likelihood of having active inflammatory lesions, a new study shows. The study, “Food Allergies are Associated with Increased Disease Activity…

The Washington University School of Medicine in St. Louis (WUSTL) will create a new research center to investigate and advance the development of tracers for positron emission tomography (PET) scans. The center, which will be established at WUSTL’s Mallinckrodt Institute of Radiology (MIR), is going to focus on the…

Microglia, the resident immune cells of the brain, were seen to change throughout the lifespan of mice in a study — and to be diverse, with distinct cell subtypes. Those with pro-inflammatory behavior may be disease-causing, as they were found to accumulate in the brains of a mouse model of…

Human mesenchymal stem cells (hMSCs), the type of stem cells present in many tissues of adults, may be manipulated to fight inflammation and used as a cell therapy to treat inflammatory diseases like multiple sclerosis (MS), a study reports. In the future, researchers plan to use animal models to…

High levels of certain lipids, or fat, in the blood are linked to increased disability scores and high levels of pro-inflammatory markers in relapsing-remitting multiple sclerosis (RRMS) patients, a small study reports. The study, “Lipoprotein markers associated with disability from multiple sclerosis,” was published in the journal Scientific…

Homotaurine, a compound proven safe for humans in long-term clinical trials, has eased autoimmune responses, brain inflammation, and multiple sclerosis-like symptoms in a mouse model of the disease, a study has found. The findings represent proof-of-principle evidence that homotaurine may represent a new potential class…

MS-specific Lineage of Oligodendrocytes May Provide New Hints on MS Development Our immune system, according to this study, may not be the only thing playing a role in the development of our MS. The same cells that produce the myelin that coats our nerves may also be…

Appropriate control of immune B-cell numbers and activation in the nervous system is key to preventing inflammation in multiple sclerosis (MS), according to a study. These findings also showed that patients with higher levels of a specific B-cell-regulating cell type had less disease activity. The study, “…

Fast Forward, a nonprofit subsidiary of the National Multiple Sclerosis Society, will invest up to $330,000 to advance the clinical development of an antibody that was shown to lessen inflammation and nerve cell damage in a multiple sclerosis (MS) mouse model. The funding will help develop the antibody (a protein…