myelin sheath

Genetically modified human umbilical cord blood cells can help nerve cells recover the myelin layer necessary for normal functioning, researchers found in a preclinical study. This finding may support the development of cell-based therapeutic approaches to help patients with spinal cord injuries or demyelinating diseases, such as multiple sclerosis (MS).

A novel imaging approach enables assessment of key nervous system deterioration in multiple sclerosis (MS), a new study in mice suggests. The research, “Development of a PET radioligand for potassium channels to image CNS demyelination,” was published in the journal Scientific Reports. MS is characterized by damage to myelin (a process called demyelination), which is an insulating sheath around axons (the long projections of neurons) that enables effective neuronal communication. As a result, patients experience a variety of symptoms, including muscle stiffness and weakness, fatigue and pain. Although existing MS medications suppress immune responses and reduce flare-ups, none can cure the disease. Despite the importance of demyelination in MS, scientists and clinicians do not currently have a way to directly image myelin damage. Magnetic resonance imaging (MRI) is used, but it does not enable the distinction between demyelination and inflammation, which are common in patients with MS. Upon myelin damage, voltage-gated potassium channels (cellular membrane proteins) become exposed. As a result, cells leak potassium, which impairs proper neuronal communication. This prompted researchers to develop a tracer that targets potassium channels. "In healthy myelinated neurons, potassium channels are usually buried underneath the myelin sheath," Brian Popko, PhD, the study’s senior author, said in a press release. Popko is a professor of neurological disorders and director of the Center for Peripheral Neuropathy at The University of Chicago. Exposed potassium channels can be targeted by the MS medication 4-aminopyridine (4-AP; dalfampridine), which partially repairs nerve conduction and mitigates MS symptoms. Using mouse models of MS, the researchers demonstrated that 4-AP binding to potassium channels is greater in demyelinated axons in comparison with well-myelinated axons. The greater binding of 4-AP led to its accumulation in damaged axons. Then, the team evaluated several fluorine-containing derivatives of 4-AP, and found that the most effective in binding to potassium channels was 3-fluoro-4-aminopyridine (3F4AP), which can be labeled with radioactive 18F. This labeling enables detection of demyelinated regions with a novel strategy based in positron emission tomography (PET). "3F4AP is the first tracer whose signal increases with demyelination, potentially solving some of the problems of its predecessors," said Pedro Brugarolas, PhD, first author of the study. Existing PET tracers bind to myelin. This translates to decreases in signal in the presence of myelin loss, “which can be problematic for imaging small lesions” Brugarolas noted. Importantly, the findings in mice were confirmed in monkeys. Experiments showed that the radiolabeled 3F4AP enters the primate brain and accumulates in areas with less myelin. Collectively, “these data indicate that [18F]3-F-4-AP may be a valuable PET tracer for detecting [central nervous system] demyelination noninvasively,” the team wrote. "We think that this PET approach can provide complementary information to MRI which can help us follow MS lesions over time," Popko said. The novel PET strategy enables the evaluation of therapies to repair myelination and also could help assess how much myelin loss is involved in other neurological disorders, such as traumatic brain injury and spinal cord injury, but also in diseases not commonly linked to demyelination, "such as brain ischemia, psychiatric disorders, and neurodegenerative diseases, including Alzheimer's," Popko concluded.

The nerve-cell-protecting myelin sheath’s failure to remove cholesterol after the membrane has been damaged limits its ability to regenerate, German researchers report. Their finding has important implications for multiple sclerosis because a hallmark of the disease is nerve cell deterioration stemming from damaged myelin. Cholesterol is a waxy, fatty substance…

A cell recycling process helps trigger an immune response against myelin, the protective layer covering nerve cell axons to aid in signal transmission, a multiple sclerosis (MS) study indicates. When University of Zurich researchers eliminated the process, mice developed much milder forms of an MS-like disease. Loss of myelin is the…

A University of Cambridge researcher, Robin Franklin, has been awarded the 2017 Barancik Prize for Innovation in MS Research for his work on myelin repair and as a potential way of treating multiple sclerosis (MS). Franklin is a senior scientist at the Wellcome Trust-MRC Cambridge Stem Cell…

A blood-clotting protein called fibrinogen prevents myelin production and blocks the neuron remyelination repair process in mice, a study finds. The study, “Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage,” appeared in the journal Neuron. Its conclusions offer new insights and…

The generation of a thin myelin sheath during remyelination — one that continues to protect nerve cells over time — is indicative of the long-term health and activity of the central nervous system (CNS) in demyelinating diseases such as multiple sclerosis (MS), a new study shows. These findings, which aim…

Researchers, using two different kinds of stem cells in rats, were able to regenerate oligodendrocytes — myelin-producing brain cells that are defective in multiple sclerosis (MS). They were also able to grow adult neural stem cells in laboratory cultures and prod them to develop into oligodendrocytes. The exact cause of MS is unknown — including what triggers attacks on myelin — but the loss of oligodendrocytes seen in the disease is known to play a role in its progression. Nerve cells in the brain send their signals through their axons, long arm-like structures that extend out from the centers of the nerve cells. The signals are electrical pulses transmitted along the length of an axon. Oligodendrocytes provide the insulation — called myelin — that wraps around axons, speeding up the transmission of electrical signals through the nerve cells. Loss or malfunction of oligodendrocytes means that signaling in the brain is impaired. It is this slowing of signaling that is thought to cause MS symptoms. Researchers from the Heinrich-Heine-University, Germany, with support from British and Chilean colleagues, designed a novel approach to regenerate oligodendrocytes, according to a press release. Stem cells are immature cells that give rise to differentiated cells — cells with a specific function, such as oligodendrocytes. Adult neural stem cells can divide and produce nerve cells and other brain cells, including oligodendrocytes. However, in normal circumstances, the regeneration of cells that take place in the human brain is not enough to repair the damage seen in MS. The researchers set out to find conditions that would promote the differentiation of adult human NSCs into oligodendrocytes. They discovered that another type of stem cell, mesenchymal stem cells (MSCs), could provide the signals required. First they tested their system in rats, and found that by using factors produced by human MSCs, they could induce the growth of new oligodendrocytes in the animals. Then they grew adult NSCs in the laboratory, and using the same factors from human MSCs were able to promote the establishment of oligodendrocytes in the cultured cells.

A herpes virus that lies dormant in many people can hinder the repair of the neuron-protecting myelin sheath whose deterioration causes multiple sclerosis, a study reports. The finding about the HHV-6 virus may help explain differences in the symptoms and progression of the disease from person to person, researchers said.

A new study on rats indicates that the antidepressant Luvox promotes the production of the neuron-protecting coating that is deficient in multiple sclerosis. It also significantly decreased the severity of the animals' disease, researchers said, adding that Luvox promoted the production of the protective coating by helping stem cells evolve into oligodendrocytes, or cells that generate what is known as the myelin sheath. Patients with MS often experience anxiety and depression, with recent studies suggesting their rate of depression is three times higher than those with other long-term medical conditions. In addition to drugs targeting the underlying mechanisms of MS, such as inflammation and myelin loss, doctors often recommend that patients take antidepressants. The most common treatments they prescribe for moderate or severe depression are a class of serotonin re-uptake inhibitors that include Luvox. Few studies have looked at antidepressants' effects on animal models of MS, however. That prompted researchers to investigate Luvox's impact on both laboratory and rat models of the disease. Researchers used embryonic neural stem cells in their study. Luvox prompted laboratory stem cells to evolve into other types of cells, including neurons, oligodendrocytes, and astrocytes, which have several roles, including supporting and repairing neurons. Prozac also promoted stem cell differentiation — but at levels 10 times higher than those of Luvox. A key finding was that that Luvox significantly decreased the severity of the disease in the rats. Another important finding was that Luvox significantly reduced demyelination and immune cell infiltration in the rats' spinal cords. It also decreased the rats' expression of pro-inflammatory proteins known as cytokines. Overall, this study “demonstrated that fluvoxamine, in addition to its confirmed role in mood disorder therapy, could serve as a candidate clinical treatment for attenuating [reducing] neuro-inflammation and stimulating oligodendrogenesis in neurological diseases, particularly MS patients.”

Regulatory T-cells in the central nervous system trigger the maturation of stem cells that increase the production of myelin at injured neurons — a discovery that places the idea of regeneration in multiple sclerosis (MS) in a whole new light. Myelin is a substance essential to the functioning of the…

When describing a multiple sclerosis exacerbation (also called a relapse, attack, or flare-up), comparing it to a home’s circuit panel is a good analogy to use. When a fuse blows on the circuit board the power is interrupted. During an MS attack, the myelin sheath that covers nerve axons…

A specific type of channel that facilitates calcium flow is needed for normal development of cells that produce a shield, called myelin, around nerve fibers — a finding that could open up new approaches to regenerating the myelin-producing cells (called oligodendrocytes) lost in multiple sclerosis (MS). Researchers now hope to…

Researchers monitoring the decomposition of an abundant brain protein, called myelin basic protein (MBP), discovered that this protein breaks down differently in people with multiple sclerosis (MS) than it does in those without the disease, particularly in two surface regions, and that difference may be the trigger for immune reactions and myelin…

Immunization with molecules present specifically in myelin may be a new approach to treating multiple sclerosis (MS), according to a recent study that found that the mouse version of such molecules could stop ongoing disease processes in an MS mouse model. The study, “Targeting Non-classical Myelin Epitopes to Treat…

The MS Society in the United Kingdom awarded £177,930 (about $217,800) to Dr. Sassan Hafizi, a researcher at University of Portsmouth, to investigate the potentially beneficial role of a central nervous system molecule, called Gas6, in repairing the myelin damage seen in patients with multiple sclerosis (MS) . Hafizi and Dr. Arthur…

The MS Society in the United Kingdom is funding a new project at the University of Glasgow, in Scotland, to examine if  heparin, a drug widely used for stroke patients, can repair neurological damage in people with multiple sclerosis (MS). MS is a progressive, debilitating, immune-mediated, neurodegenerative disorder in which…

Therapies aimed at regenerating the myelin sheath can work to restore proper brain activity and may be a viable way of treating multiple sclerosis (MS), according to researchers at the University of California San Francisco. In the study, “Accelerated Remyelination During Inflammatory Demyelination Prevents Axonal Loss And Improves Functional Recovery,” published…

In multiple sclerosis (MS), scientists have long believed that the body’s own immune system attacked myelin sheaths, the “insulating tape” that surrounds neurons, causing the disease. But researchers at Tel Aviv University are challenging that view, in a study reporting that MS may in fact be triggered by an instability inherent in the myelin membranes. The…

Tamoxifen (brand name, Nolvadex), a widely used treatment for breast cancer, can also be used to treat myelin loss in patients with multiple sclerosis (MS), a new study suggests. The finding, by a team of researchers at the University of Cambridge, U.K., was published in a study titled “…

As Multiple Sclerosis News Today reported in mid-July, Endece Neural was issued an additional U.S. patent for its lead investigational product, NDC-1308. The drug is under development to repair the myelin sheath damaged in multiple sclerosis (MS), a major causing disease progression and increasing disability. The sheath, an…

Oligodendrocytes — brain cells that wrap themselves around neurons to produce myelin — are much more diverse than previously believed. Scientists in Sweden, using a new type of sequencing, have discovered more than a dozen different kinds, including an oligodendrocyte subtype involved in motor learning, a finding that might spur new research into protecting…

Researchers at the University of Buffalo’s Hunter James Kelly Research Institute (HJKRI) discovered that the cells that form myelin in the nervous system respond to mechanical stimulation by activating molecules from a specific pathway, which are transferred to the nucleus, triggering myelination. The findings, which may be key to developing new therapies…

The evolution of the myelin sheath throughout childhood has been visualized in vivo for a first time, according to findings reported in the study “Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging,” published in the journal NeuroImage. To function well, nerve cells in the brain rely on…

Researchers have described the mechanisms by which cell precursors of oligodendrocytes — the cells responsible for the generation of myelin in the central nervous system — migrate from their birthplace to their workplace during brain and spinal cord development, and begin to mature and wrap about nerve fibers. The finding, the authors…

A study from the University of Cambridge showed that the membrane-bound signaling protein EphrinB3, which acts by inhibiting the maturation of oligodendrocytes, also blocks the remyelination of damaged neurons in multiple sclerosis (MS). The study, “Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS re-myelination,“ uncovered a new target to explore…

Japanese scientists have discovered new information about how the myelin sheath is repaired following damage. Myelin is a fatty substance that wraps around nerve cells and helps them to conduct impulses. The research could have major implications for how multiple sclerosis is understood and even treated. The study, titled “Inactivation…

Image credit: Yaming Wang/Bernd Zinselmeyer A new study has shown that a protein called TREM2 may inhibit microglial repair of damaged myelin in multiple sclerosis. The study appeared in the Jan. 29 issue of Acta Neuropathologica. MS is characterized by the degeneration of myelin, a fatty…