myelin

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 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…

Cleveland Clinic Neurologist Applauds Mayzent’s FDA Approval, But Surprised by Those It May Not Treat When I wrote my “MS Wire” column a few days after Mayzent’s approval, I wondered why the FDA had OK’d the medication for active secondary progressive multiple sclerosis (SPMS), but not…

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…

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…

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…

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 “New MS Therapy Company to Focus on Rejuvenating Coating…

In mapping the immune system of the brain in mice and humans, scientists in Germany found that microglia — a type of nerve cell located in the central nervous system and responsible for supporting and protecting neurons — share the same core design, but behave differently depending on the specific function each…

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…

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.”…

MS Patients Sought to Test Alternative Chronic Pain Treatment Methods Do you have serious pain issues along with your MS? If so, you might be interested in this study that’s looking for participants. By the way, who says that pain isn’t an MS symptom? A clinical trial…

Stem cells tweaked in the laboratory have allowed researchers, reportedly for a first time, to generate and maintain ball-shaped cultures — called spheroids — of human brain cells in 3D that contain oligodendrocytes, the cells that produce myelin, along with neurons and the astrocytes that are essential to nerve cell health.

Subpopulations of oligodendrocytes — cells that produce the myelin sheath that protects nerve fibers — are altered in patients with multiple sclerosis, a study shows. These findings suggest that oligodendrocyte diversity and the different functions of these subpopulations might have a greater role in the disease than previously thought. The severity of MS varies greatly, and the patient's disability level does not correlate well with the degree of myelin loss. This suggests that other factors contribute to MS severity. One such factor may be that oligodendrocytes are heterogeneous — diverse in makeup and function. For example, oligodendrocytes in mouse spinal cords are known to naturally produce longer myelin sheaths than oligodendrocytes in the mouse brain. Additionally, individual oligodendrocytes have been shown to have different molecular makeups. However, the extent of human oligodendrocyte diversity and its possible contribution to MS pathology remains unknown. Researchers from the Karolinska Institutet and the MRC Centre for Regenerative Medicine studied the differences of individual human oligodendrocytes from healthy and MS brains to assess their diversity. Specifically, the team examined oligodendrocytes from the white matter areas of post-mortem human brains both from MS and non-MS patients. The team examined the RNA content — the messenger molecule carrying instructions from DNA for the production of proteins — from individual oligodendrocytes. Researchers identified groups of RNA molecules that defined features of oligodendrocytes from healthy human white matter. Some of these groups match those that defined oligodendrocytes in healthy mice. Strikingly, some of these RNA molecules in healthy brains were under-represented in oligodendrocytes from MS brains, whereas others were more prevalent. “We found that oligodendrocytes are a diverse population of cells and that different types are likely to have different functions in the brain,” Charles ffrench-Constant, the study's co-lead author, said in a Karolinska Institutet news release written by Katarina Sternudd. These differences in oligodendrocyte RNA content may indicate different functional states of oligodendrocytes in MS lesions. “The proportions of different resident oligodendrocytes in the lesions are changed, along with their properties, suggesting that they might have important roles in MS,” said Eneritz Agirre, PhD, a study co-author. Furthermore, the researchers believe that this altered diversity in oligodendrocytes in MS may be important to understand disease progression and develop therapeutic approaches. “Understanding which types of oligodendrocytes are most beneficial in repairing myelin will be crucial for maximizing the chances of developing much-needed treatments for MS,” said Anna Williams, PhD, study co-lead author. The team concluded that the changes in different oligodendrocyte subpopulations in MS suggest "a more complex role of these cells in the pathology of the disease, but also in regeneration of new cells,” said Gonçalo Castelo-Branco, PhD, another study co-lead author.

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…

A protein marker for activated immune cells called Chi3I3 is key for the production of myelin-forming cells, and may become a target to boost myelin repair in multiple sclerosis (MS), according to a new study. The research, “Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune…

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…

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 …

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…

Inactivation of S1PR2, a cell surface protein, helps improve clinical disability and reduce demyelination in a mouse model of experimental autoimmune encephalitis (EAE), a condition similar to multiple sclerosis (MS) in humans, a study shows. This finding suggests that therapies blocking S1PR2 could have the potential to treat MS. The…

The formation of new myelin sheaths by oligodendrocytes is impaired in the absence of a small molecule, called Vav3, that oversees pathways regulating the shape of oligodendrocytes, new study reports. Its researchers pinpoint Vav3 as a potential therapeutic target to improve and speed myelin repair in diseases like multiple sclerosis…

Mature, adult oligodendrocytes can reacquire their ability to produce myelin to replace the ones lost in diseases like multiple sclerosis (MS) without undergoing a stem cell-like state, a new study shows. Myelin is the fat-rich substance that wraps around nerve fiber projections (axons) protecting them and increasing the speed of…

The cells that produce myelin in the brain and spinal cord, called oligodendrocytes, may play an active role in the onset or progression of multiple sclerosis (MS), according to a study combining data from MS mouse models and the human brain. This discovery supports the…

Blocking SARM1, a protein identified as a central mediator of nerve cell degeneration, works to prevent damage to axons — nerve cell fibers essential in cell-to-cell communication — and may be a way of treating neurodegenerative diseases like multiple sclerosis (MS), data from Disarm Therapeutics shows. Specially, genetically deleting…

Myelin loss might be prevented by astrocytes, a brain cell that regulates myelin’s thickness in coating nerve fibers to support the proper transmission of nerve signals, after astrocytes were seen to block an enzyme called thrombin in a study from the National Institutes of Health (NIH). Its…

Environmental changes, such as high temperatures and alterations in salt types and concentrations, trigger structural changes to myelin that may increase the risk of multiple sclerosis (MS), according to a new study. The research, “Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions,” was…

An antibody that blocks a blood-clotting factor from leaking into the brain was seen to lessen neuroinflammation and nerve cell damage in mouse models of multiple sclerosis (MS) and Alzheimer’s disease. Scientists developed an antibody that selectively inhibits the inflammation-triggering capacity of fibrin in…

An enzyme produced by bacteria in the gut was seen to activate immune cells linked to the development and progression of multiple sclerosis, a finding that may pave the way for a vaccine that might alter autoimmune mechanisms involved in MS. The study, “…

Treating relapsing-remitting multiple sclerosis (RRMS) patients with GeNeuro’s investigational compound GNbAC1 lessened brain atrophy and lesion load and suggested myelin preservation, according to results of a Phase 2b study. Importantly, monthly intravenous GNbAC1 administration for 48 weeks also had neuroprotective effects in the study’s inactive population, which refers…

A new subtype of multiple sclerosis (MS) — called myelocortical MS (MCMS) — is characterized by cortical neuronal loss, but not by loss of myelin in the brain’s white matter, according to a study. Research on this new type of MS was presented today at the 34th congress of…

Jonathan Kipnis, the researcher who discovered that lymphatic vessels are important mediators of the underlying molecular mechanism of multiple sclerosis (MS), has received the prestigious Director’s Pioneer Award from the National Institutes of Health (NIH). This prize recognizes researchers who have made important contributions to the development of new…