myelin

Researchers have identified a new subtype of multiple sclerosis (MS), one marked by nerve cell degeneration that occurs independently of immune system attacks against myelin, a process known as demyelination and considered a hallmark of MS. The new subtype — called myelocortical MS — is indistinguishable from others in the…

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…

Removing a specific microRNA molecule — miR-150 – eased disease severity, inflammation, and loss of myelin in a mouse model of multiple sclerosis (MS), researchers report. Their study, “Silencing miR-150 Ameliorates Experimental Autoimmune Encephalomyelitis,” was published in the journal Frontiers in Neuroscience. Micro RNAs (miRNAs) are…

Researchers at Case Western Reserve University School of Medicine have developed a cutting-edge laboratory technique able to turn human stem cells – special cells able to grow into any type of cell in the body – into brain-like tissues in a culture dish. They intend to use their tool to study how myelination – the deposition of myelin around nerve cells – occurs in the central nervous system, and how diseases such as multiple sclerosis (MS) impair this process. The experimental protocol to grow these structures outside an organis) is described in the study, "Induction of myelinating oligodendrocytes in human cortical spheroids," published in the journal Nature Methods. These structures, called “oligocortical spheroids,” are small spheres that contain all the major cell types usually found in the human brain, including oligodendrocytes — cells that produce myelin, which is the fatty substance that insulates nerve fibers. Previous cerebral organoid techniques failed to include oligodendrocytes. “We have taken the organoid system and added the third major cell type in the central nervous system — oligodendrocytes — and now have a more accurate representation of cellular interactions that occur during human brain development,” Paul Tesar, PhD, associate professor of genetics and genome sciences at Case Western's medical school and the study's senior author, said in a press release. Oligodendrocytes are essential to good brain health. Without these cells, myelin production is hampered and nerve cells cannot communicate effectively, and eventually they start to deteriorate. This is the starting point for many neurological disorders caused by myelin defects, including MS and rare pediatric genetic disorders like Gaucher disease. Using this new organoid system and these myelin-producing cells, researchers intend to study the process of myelination — how it occurs in normal circumstances and how neurodegenerative diseases disrupt this process. “This is a powerful platform to understand human development and neurological disease,” Tesar said. “Using stem cell technology we can generate nearly unlimited quantities of human brain-like tissue in the lab. Our method creates a ‘mini-cortex,’ containing neurons, astrocytes, and now oligodendrocytes producing myelin. This is a major step toward unlocking stages of human brain development that previously were inaccessible.” Researchers not only demonstrated that they were capable of generating mature oligodendrocytes derived from human stem cells in vitro, but they also showed these cells were able to exert their function and produce myelin starting at week 20 in a culture dish. Their improved organoid system could also be used to test the effectiveness of potential myelin-enhancing treatments. “These organoids provide a way to predict the safety and efficacy of new myelin therapeutics on human brain-like tissue in the laboratory prior to clinical testing in humans,” said Mayur Madhavan, PhD, co-first author on the study. To prove this point, researchers treated organoids with promyelinating compounds known to enhance myelin production in mice, and measured the rate and extent of oligodendrocyte generation and myelination. Under normal conditions, adding promyelinating drugs to cultured organoids increased the rate and extent of oligodendrocyte generation and myelin production, the team reported. But results differed in important ways using diseased organoids.  Specifically, treating organoids generated from patients with Pelizaeus-Merzbacher disease — a fatal genetic myelin disorder — brought an in vitro recapitulation of the patients' symptoms. “Pelizaeus-Merzbacher disease has been a complicated disorder to study due to the many different mutations that can cause it and the inaccessibility of patient brain tissue,” said Zachary Nevin, PhD, co-first author on the study. “But these new organoids allow us to directly study brain-like tissue from many patients simultaneously and test potential therapies.” Altogether, these findings demonstrate that oligocortical spheroids could be a versatile in vitro system to study how myelination occurs in the central nervous system, and a possible model for testing new therapies for neurodegenerative disorders. “Our method enables generation of human brain tissue in the laboratory from any patient,” Tesar said. “More broadly, it can accurately recapitulate how the human nervous system is built and identify what goes wrong in certain neurological conditions.”

Therapy candidates that block enzymes responsible for making cholesterol can promote myelin regeneration, a discovery that could lead to new regenerative medicines capable of treating multiple sclerosis (MS) and other neurological diseases, according to a study. In fact, Convelo Therapeutics plans to do just that, announcing its intention to use…

Activation of the immune response mediated by cells called microglia favors remyelination and myelin repair in multiple sclerosis (MS), according to a new Canadian study using mice. The research, “mCSF-Induced Microglial Activation Prevents Myelin Loss and Promotes Its Repair in a Mouse Model of Multiple Sclerosis,” was…

A better understanding of the processes behind a continual and healthy renewal of myelin — the fatty, protective substance wrapping nerve cell fibers — may now exist. Researchers identified an enzyme, called PRMT5, that they believe regulates the number of myelin-producing cells in the brain and spinal cord. Their discovery…

Blocking a protein receptor called muscarinic type 3 (M3R) could be an effective way to promote remyelination in multiple sclerosis (MS) patients, according to a State University of New York at Buffalo (UB) study in mice. The research, “Muscarinic receptor M3R signaling prevents efficient remyelination by…

A common anti-parasitic agent showed a potential to prevent inflammation and to promote nerve cell recovery — remyelination — in a mouse model of multiple sclerosis (MS). By promoting the activity of a receptor called P2X4R that is present in microglial cells — immune cells that reside in the brain…

An investigational cannabidiol-derived compound called EHP-101 may help to boost remyelination, prevent nerve cell damage and lower the reactivity of microglia cells — immune cells of the brain and spinal cord — a  study in mouse models of multiple sclerosis (MS) reports. EHP-101, being developed by Emerald Health…

A new fluorescent imaging strategy allows researchers to track T-cells and further understand their dynamics in vivo, giving them insight into what happens when these immune cells attack myelin in a mouse model of multiple sclerosis (MS). The new technology was reported in the study, “A timer for…

Discovery of ‘Fiery’ Cell Death Mechanism May Be MS ‘Game-Changer’ Researchers at the University of Alberta have discovered a process that may be responsible for destroying myelin. Better than that, they also think they have a way of limiting that process using a medication. The inhibitor, known…

Researchers have unveiled a new cell death mechanism called pyroptosis — also known as “fiery death” — as a main factor driving neurodegeneration and loss of myelin in people with multiple sclerosis (MS). An inhibitor of pyroptosis, currently undergoing testing in human clinical trials for epilepsy, decreased central nervous system inflammation…

Chemical that Stimulates Estrogen Receptors Seen to Promote Myelin Repair Through ‘Good’ Inflammation in Mouse MS Model Caution: This is only a mouse study. However, anything that might repair the damaged myelin of people with MS catches my eye. In this case, researchers are building on earlier…

A chemical compound called indazole chloride promotes repair of myelin, the protective layer of nerve fibers, through “beneficial” inflammation in a mouse model of multiple sclerosis (MS), a study reports. The preclinical research, “Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in…

Infection with lymphocytic choriomeningitis virus triggers expression of a factor called TOX in immune cells strengthening their migration into the brain and promoting damaging effects, including inflammation and tissue destruction. These findings represent a new piece of the puzzle about the mechanism underlying autoimmune diseases  like multiple sclerosis (MS).

Organizations Join Forces to Launch New Adventure Program for Young MS Patients It seems we too often ignore the needs of younger people who have MS. (I’ve written a couple of columns about this.) This program isn’t a medical approach, but it may serve some other…

A molecule responsible for preventing the repair of white matter in the brain, a process critical to treating multiple sclerosis (MS) and cerebral palsy, has been identified. The research, “A TLR/AKT/FoxO3 immune-tolerance like pathway disrupts the repair capacity of oligodendrocyte progenitors,” was published in The Journal…

Subtle changes in myelin, the protective layer of nerve fibers, may be an early event in multiple sclerosis (MS) prior to the inflammatory reaction, a new University of Calgary study shows. The study, “Biochemically altered myelin triggers autoimmune demyelination,” was published in the journal Proceedings…

A new company called Pipeline Therapeutics will focus on developing next-generation therapies for regenerating the key nerve-protection process that is damaged in multiple sclerosis. Roche, Inception Sciences, and the venture capital firm Versant Ventures laid the groundwork for Pipeline by establishing a partnership in June 2014 that formed the…

Emerald Health‘s investigational cannabidiol-derived EHP-101 reduces neuroinflammation, the risk of loss of myelin, and nerve cell damage in two mouse models of multiple sclerosis (MS), a new study shows. These results support the potential therapeutic benefits of EHP-101 for MS, and Emerald Health Pharmaceuticals expects to launch a human…

New Spherix Report Finds PPMS Treatment Increased Significantly in Past Year Primary progressive MS has, in some eyes, been the stepchild of the disease-modifying therapies. PPMS patients move steadily downhill, and some believe treatments haven’t kept pace with their disease. Now, the research company Spherix has news…

High levels of a protein called calnexin in the brain may disrupt the blood-brain barrier of patients with multiple sclerosis, a Canadian study suggests. The finding could lead to new treatment strategies to prevent brain damage in MS. The research, “Calnexin is necessary for T cell…

One way the body may protect itself from nerve cell inflammation is to have cells in the blood-brain barrier increase their production of a protein that keeps immune cells from entering the brain, researchers in Germany and Canada report. The finding suggests that scientists could develop a multiple sclerosis therapy around the protein, known as EGFL7. It would work by preventing as many inflammation-generating immune cells from entering the brain. The underlying trigger for MS is immune cells crossing the blood-brain barrier to invade the central nervous system (CNS). The barrier is a selective membrane that shields the CNS from general blood circulation. Therapies that prevent immune cells from entering the brain can help control the disease, studies have shown. They include Tysabri (natalizumab, marketed by Biogen). But “as with other highly effective disease-modifying therapies which influence a broad range of peripheral immune cells, potential devastating adverse events limit the use of this therapy as a first-line agent,” the researchers wrote. The team at Mainz University Medical Center in Germany and the University of Montreal wondered if epidermal growth factor-like protein 7 (EGFL7) could prevent the brain inflammation in MS.  Although scientists had not previously linked it to MS, it was shown to regulate the migration of immune cells into breast cancer tumors. The CNS response to the chronic inflammation seen in MS patients and a mouse model of the disease was to increase EGFL7 in the blood-brain barrier, the researchers found. Researchers said the increase prevented pro-inflammatory immune cells from crossing into the CNS. Endothelial cells that line blood capillaries in the blood-brain barrier are the ones that secrete EGFL7. “We postulate that EGFL7 upregulation by BBB-ECs [brain blood barrier-endothelial cells] is induced as a compensatory mechanism to promote survival and recovery of BBB function in neuroinflammatory conditions,” the team wrote. Researchers then tested what happened in mice that lacked EGFL7. They found that the mice developed MS earlier and that their blood-brain barrier membrane was less efficient at keeping immune cells out. Treatment with EGFL7 improved the disease severity in the MS mice and tightened the blood-brain barrier, they said. “In light of our findings, smaller EGFL7 agonists, in development for other diseases, could therefore constitute an appealing therapeutic avenue for MS,” the team concluded.

Inhibiting an oxidative stress enzyme reduced nerve cell damage and promoted the formation of new nerve cells, a multiple sclerosis study in mice showed. It also helped regenerate cells that produce the nerve cell-protecting myelin sheath, researchers said. The team used a mouse model of the progressive form of MS in…

Pilot Study Is Testing Whether Mediterranean Diet Can Help MS Patients There’s been a good deal of news recently about the possibility that bacteria in our stomachs have an impact on our MS. There’s also been talk, for a long time, about whether certain diets can improve…

University at Buffalo researchers are working on ways to improve multiple sclerosis patients’ cognitive function and to repair damage to the mylein coating that protects nerve cells. The National Multiple Sclerosis Society awarded the researchers more than $1.1 million to conduct the studies. One, “The Effects of Working Memory…

Stem Cell Treatment Benefits Three-fourths of MS Patients in Phase 1 Trial This is encouraging news for MS patients hoping to see some action in the stem cell area. A Phase 1 mesenchymal stem cell trial is reporting positive results, and a Phase 2 trial is underway in…

Inhibiting an enzyme responsible for turning genes on and off can reverse damage to the myelin sheath that protects nerve cells, improving limb function, a multiple sclerosis-related study in mice shows. The research, which involved mice with sciatic nerve damage rather than MS, was published in the journal Nature Medicine.

Clene Nanomedicine says its pre-clinical studies demonstrate the remyelination effects of CNM-Au8, supporting its potential to treat multiple sclerosis (MS) and other demyelinating disorders. Clene presented its data in a session, “Nanocrystalline Gold As a Novel Remyelination Therapeutic for Multiple Sclerosis,” that took place at the third annual Americas…