MS lesions

When a doctor orders an MRI with contrast, gadolinium is usually the contrasting agent used. Gadolinium is injected into the patient’s vein after the radiologist takes the first round of MRI images. This helps the radiologist receive sharper, more readable images. In the case of multiple sclerosis (MS),…

Levels of a protein stemming from brain cell damage can mirror the severity and symptoms of multiple sclerosis, an analysis of combined data from three trials showed. Researchers will present this and related findings at the annual meeting of the American Academy of Neurology in Los Angeles, April 21-27. The…

Genentech’s Ocrevus (ocrelizumab) reduces levels of cerebrospinal fluid biomarkers that denote nerve cell damage in multiple sclerosis patients, a Phase 3 clinical trial shows. Researchers will present the results at the American Academy of Neurology’s annual meeting in Los Angeles, April 21-27. The presentation will be titled “Interim Analysis of the…

Professor Frederik Barkhof, MD, PhD, has won the 2018 John Dystel Prize for Multiple Sclerosis Research for pioneering the use of magnetic resonance imaging (MRI) to improve multiple sclerosis (MS) diagnosis and understanding of the disease. The prize, decided by a peer committee, is awarded annually by…

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…

Editor’s note: Tamara Sellman continues her occasional series on the “MS alphabet” with this column referencing terms starting with the letters “Q” and “R.” Symptoms of MS Quadrantanopia This eye-related symptom of MS refers to the compromising of vision in one of the quarters of the visual field,…

Symbiotix Biotherapies has gained access to Harvard University material that could help it develop treatments for autoimmune and inflammatory diseases like multiple sclerosis and inflammatory bowel diseases. It obtained access to the intellectual property, much of which deals with gut bacteria, under a licensing agreement with Harvard. Intellectual property typically includes…

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…

Merck KGaA’s evobrutinib led to significant reductions in relapsing multiple sclerosis patients’ brain and spinal cord lesions, compared with a placebo, a Phase 2b clinical trial showed. Researchers measured the number of lesions at weeks 12, 16, 20 and 24. Evobrutinib, also known as M2951, is an oral inhibitor of…

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…

United Arab Emirates scientists have found active Epstein-Barr virus in many multiple sclerosis patients’ brain cells, supporting the notion that it plays a role in the disease. The team found it in two types of brain cells — astrocytes and microglia. The virus can be active or lie dormant in…

Degeneration of the brain’s deep gray matter is associated with more rapid disability in multiple sclerosis patients, a European study shows. The research, “Deep gray matter volume loss drives disability worsening in multiple sclerosis,” was published in the journal Annals of Neurology. Scientists know that loss…

A combination of an anti-viral therapy and the anti-depressive mirtazapine can stop the worsening of an infection linked to the multiple sclerosis therapy Tysabri (natalizumab), a case study suggests. The infection, John Cunninghan polyomavirus, can cause a potentially fatal brain infection known as  progressive multifocal leukoencephalopathy, or PML. Both…

Celgene’s Ozanimod reduces relapsing multiple sclerosis patients’ relapses, brain lesions, and brain volume loss, a Phase 3 clinical trial shows. The company presented the results of the SUNBEAM trial at the ACTRIMS Forum 2018 convention in San Diego, Feb. 1-3. The presentation was titled “Ozanimod Demonstrates Efficacy and Safety…

Extending the dosing periods of Tysabri (natalizumab) treatment may help reduce the risk of progressive multifocal leukoencephalopathy, or PML, in multiple sclerosis (MS) patients infected with the JC virus, a study suggests. The study, “Natalizumab Extended Interval Dosing Is Associated with a Reduction in Progressive Multifocal Leukoencephalopathy…

Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this column referencing terms starting with the letter “P.” This column is fifth in a series of seven. Symptoms of MS Plaque This is one of the common…

TG Therapeutics‘ ublituximab (TG-1101) led to a remarkable reduction in multiple sclerosis patients’ brain and spine lesions, a Phase 2 clinical trial showed. In fact, none of the treated patients had new gadolinium-enhancing lesions — or damaged nerve cell areas — six months after treatment, researchers said. Their analysis covered patients…

One single session of non-invasive brain stimulation can reduce cognitive fatigue in patients with multiple sclerosis (MS), say researchers at Germany’s Otto-von-Guericke University Magdeburg. Their study, “Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis,” appeared in the…

Multiple sclerosis patients have high levels of a protein called osteopontin in their cerebrospinal fluid and blood, making it a potential tool for diagnosing the disease and predicting its course, a study suggests. The research, “Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis,” was published in the journal PLOS One. Researchers wanted to know if levels of osteopontin in cerebrospinal fluid and blood could be a reliable biomarker for MS. To arrive at answer, they “conducted a systematic review and meta-analysis" of studies that had measured the protein's levels in cerebrospinal fluid and blood "in MS patients and controls." The team searched for studies in three databases — PubMed, Web of Science and Scopus. Out of 27 that met their criteria, they used 22 in the meta-analysis. All four types of MS were represented in the studies — clinically isolated syndrome, relapsing-remitting MS, secondary progressive MS, and primary progressive MS. There were three types of controls in the articles — healthy people, people with non-inflammatory neurological disorders, and people with inflammatory neurological disorders. Researchers' first observation was that all of the MS patients had higher levels of osteopontin than controls. The protein's levels were significantly higher in relapsing-remitting MS patients than in those with clinically isolated syndrome, the group with the lowest osteopontin levels. Levels were similar in the other types of MS. Patients with an active disease had significantly higher levels of the protein in their cerebrospinal fluid than those with a stable disease. The results supported previous studies' findings that osteopontin levels are higher than normal in the cerebrospinal fluid and blood of MS patients, strengthening the notion that it could be used as a biomarker for MS. “Given the fact that OPN [osteopontin] levels are higher during relapses, we think that by monitoring this biomarker,  we might be able to predict the disease course," the team wrote. "We propose that developing drugs modulating OPN concentration may be a new treatment strategy for MS."

Multiple sclerosis patients with central nervous system pain have high levels of a protein known as nerve growth factor in their cerebrospinal fluid, a study shows. The research, “Nerve growth factor is elevated in the CSF of patients with multiple sclerosis and central neuropathic pain,” was published…

Deep grey matter volume loss in the brain drives multiple sclerosis (MS) progression and disability, and is particularly evident in people with progressive forms of the disease, a retrospective multi-center study suggests. The study “Deep grey matter volume loss drives disability worsening in multiple sclerosis” was published in…

New research shows how a high-salt diet leads to excessive levels of interleukin-17 (IL-17) in multiple sclerosis (MS) patients, causing changes in endothelial cells that result in dementia. These findings suggest that therapeutics targeting IL-17 may help halt the neurovascular damages of MS and other autoimmune diseases linked to high…

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 Food and Drug Administration (FDA) issued a safety alert about gadolinium, the dye that’s injected when our doctors order a brain MRI “with and without” contrast. The dye provides the contrast that “lights up” areas of MS inflammation in the brain. But the FDA advisory is…

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…

As we all know, MS is difficult to diagnose. Put another way, it’s easy to misdiagnose. There’s no single diagnostic test for MS. Neurologists use their clinical examination, the patient’s medical history, and lab tests. They also rely on MRI imaging of the brain and sometimes of 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…