European Commission Approves Ocrevus to Treat RRMS, PPMS Throughout EU This is a biggie. It’s been nearly a year since the FDA approved the use of Ocrevus here in the U.S. Finally, it’s been given the green light in Europe. Canada, Australia, Switzerland, and various countries in…
myelin
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.
A combination therapy of low-dose methylprednisolone and interferon (IFN)-beta-secreting stem cells is effective in a mouse model of multiple sclerosis (MS), a new Korean study suggests. The research, “Effective combination of methylprednisolone and interferon β-secreting mesenchymal stem cells in a model of multiple sclerosis,” appeared in the…
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…
Researchers at GlaxoSmithKline (GSK) have identified the histamine receptor 3 (H3R) as a potential new therapeutic target for promoting remyelination in patients with multiple sclerosis (MS). Their study “Histamine Receptor 3 negatively regulates oligodendrocyte differentiation and remyelination,” appeared in the journal PLOS One. Regrowth of myelin is known as…
Tailored molecular treatments for specific disabilities may be a breakthrough for multiple sclerosis (MS) patients, finds a new study by researchers at University of California-Los Angeles (UCLA). The study, “Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes,” appeared in the journal Proceedings…
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 natural metabolite called taurine may boost the effectiveness of existing multiple sclerosis (MS) therapies, researchers say. Taurine helps oligodendrocytes, which are cells responsible for myelin production, to fully mature and activate the remyelination process of damaged nerve cells. The findings were reported in the study, “…
Protamine — an agent used to stop the anticoagulant effects of heparin — was seen to trigger remyelination in mice with myelin damage. But while pointing a way forward for studies of myelin regeneration in multiple sclerosis (MS), the research team underscored that protamine itself is not an optimal treatment candidate.
The Mayo Clinic has developed a test that allows doctors to distinguish other inflammatory demyelinating diseases from multiple sclerosis in the early stages of a disorder. The test, the first of its kind in the United States, looks for an antibody against a protein known as myelin oligodendrocyte glycoprotein…
Immune cells that destroy myelin in multiple sclerosis (MS) access the brain and spinal cord via two different routes, a new mouse study shows. This suggests that therapies which target these entry routes may shield the brains of MS patients from further damage. The study, “Caveolin1 Is Required for…
Myelin-producing Brain Cells Regenerated Using Stem Cells in Early Study We know that when the myelin coating of our nerve axons is destroyed, MS symptoms result. So a process that halts or reverses that destruction is the goal of a lot of MS research. This is a…
Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this first of two columns about terms starting with the letter M. Symptoms of MS Memory problems Memory loss is a common complaint for people with MS. Even for those with no physical or…
Targeting Blood-clotting Protein Can Restore Brain’s Potential to Repair Myelin Layer, Study Shows
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…
MS News That Caught My Eye Last Week: Older Patients, Stem Cells, Myelin, B-cells vs. T-cells
#MSParis2017 – Trial to See if Disease-modifying Therapies Not Necessary in Older MS Patients This tops my list this week because, at age 69, I certainly fit the definition of an “older” MS patient. The study is hoping to enroll 300 MS patients in the U.S. who…
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.
GeNeuro‘s humanized antibody GNbAC1 promotes the rejuvenation of the myelin coating that protects nerve cells in patients with relapsing-remitting multiple sclerosis, or RRMS, a Phase 2 clinical trial shows. The treatment is also safe, the study showed. Dr. Hans-Peter Hartung of the Heinrich-Heine-University Düsseldorf in Germany presented the results at the 7th…
The Japanese company MediciNova‘s anti-inflammatory agent ibudilast slows multiple sclerosis patients’ brain shrinkage and their loss of the protective myelin coating around nerve cells, a Phase 2 clinical trial shows. Robert J. Fox of Ohio’s Cleveland Clinic Neurological Institute presented the results at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, Oct. 25-28.
Inhibiting a protein found at high levels in immune cells located in the brain can rejuvenate myelin, the protective coating around nerve cells, according to a multiple sclerosis study in mice. Blocking the protein, known as the colony-stimulating factor 1 receptor, or CSF1R, can also prevent the immune cells from…
People with a demyelinating disease associated with antibodies against a myelin oligodendrocyte glycoprotein (MOG), most often develop episodes of optic neuritis (inflammation of the optic nerve) that can be treated with corticosteroids, according to data presented today at the 7th Joint ECTRIMS-ACTRIMS Meeting from Oct. 25-28 in Paris. MOG antibody-associated demyelination is a…
There’s been some internet buzz recently about the possibility of an over-the-counter allergy drug that helps to repair the myelin that MS damages. The drug is clemastine fumarate, and I suspect that some of that buzz may have been generated by headlines found on Twitter and…
Common Allergy Treatment Restores Protective Neuron Coating in MS, Trial Suggests This is the kind of news we all hope to hear. A treatment that will repair our frayed “wires” and, in doing so, restore some of the function that MS has stolen from us. This is…
Scientists have been trying to find a way to restore a protective covering around nerve cells whose loss leads to the neuron damage associated with multiple sclerosis. A team at the University of California, San Francisco may have found a way to do it. And perhaps surprisingly, the possible solution…
Groundbreaking evidence of the existence of lymphatic vessels in the human brain could answer the question of how the brain gets rid of waste products, and holds clear implications for neuroinflammatory disorders such as multiple sclerosis. The lymphatic system is a network that helps the body to rid itself of toxins and waste products. Lymphatic vessels, which are similar to blood vessels, transport a clear fluid – lymph – which is filtered in lymph nodes. It has long been thought that the brain lacks lymphatic vessels. However, a team of researchers at the National Institutes of Health (NIH), building on previous research in rodent brains, recently found evidence that the brain may actually drain waste through lymphatic vessels. The researchers injected healthy volunteers with a magnetic dye called gadobutrol, which is usually used as a contrast agent to image blood vessels. They then scanned the brains of these individuals using magnetic resonance imaging (MRI) under specific settings. This allowed them to view the dye within the outer layer of the brain, known as the dura. The MRI revealed that the dye was visible both as dots and straight lines, which might indicate lymph vessels. This suggested that the dye leaked out of blood vessels into the dura and were later 'picked up' by lymphatic vessels. These vessels were not seen when the volunteers were injected with another dye that does not leak out of blood vessels. Evidence of lymphatic vessels in the brain was also found in autopsied human brain tissue. Although a pair of 2015 studies had shown evidence of lymphatic vessels in the brains of mice, this is the first study that demonstrates that a similar system exists in human brains. “For years we knew how fluid entered the brain. Now we may finally see that, like other organs in the body, brain fluid can drain out through the lymphatic system,” Reich said . In addition to changing the way we think about the lymphatic system and the brain, this study lays the foundations for future research to investigate whether the function of the lymphatic system is altered in the brains of patients with multiple sclerosis or other disorders affecting the nervous system.
A substance that the pancreas secretes can promote the regeneration of the protective nerve-cell coating that is damaged in multiple sclerosis, a mouse study shows. The substance is fibroblast growth factor 21, or FGF21. It promotes remyelination, the renewal of the myelin sheath protecting the central nervous system, according to the…
Multiple sclerosis damages human brains, so MS researchers often study mice brains. How can multiple sclerosis be cured or prevented without studies of human brains? Researchers need the anatomical bequests of MS brains. Harvard Brain Tissue Resource Center Harvard University specifically collects and studies brains (and brain tissue),…
In case you missed them, here are some news stories that appeared in MS News Today that caught my eye over the past week: Q Therapeutics Approved to Start Trial of Cell Therapy Aiming to Restore Myelins Those of us with MS know that if something can…