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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 high relapse rates but less physical impairment before starting on  Novartis’ Gilenya (fingolimod) are likely to experience a surge in disease activity if they stop the treatment, researchers in Turkey report. The study, which dealt with patients with relapsing forms of MS, referred to the surge as "severe disease reactivation," or SDR. Researchers published their article, “Factors Predictive of Severe Multiple Sclerosis Disease Reactivation After Fingolimod Cessation,” in the journal The Neurologist. Studies have shown that Gilenya, which the U.S. Food and Drug Administration approved in 2010, can benefit adults with relapsing MS. It reduces annualized relapse rates and prevents more brain lesions from forming, compared with standard interferon treatments. Lesions are damaged nerve cell areas. Despite its benefits, Gilenya is not recommended for patients with heart or liver problems, low levels of white blood cells, severe herpes virus infections or other infections. Also, patients who do not respond to Gilenya and women who are planning to become pregnant are advised to stop the treatment. Discontinuing Gilenya can lead to a return to pretreatment disease activity, or severe disease reactivation, in some patients. It is unclear why this happens and why it affects only some patients. To better understand what risk factors could be associated with reactivation, a team at Istanbul University compared the demographic and disease features of patients who developed SDR after stopping treatment with Gilenya. SDR was defined as including these elements within 6 months of Gilenya discontinuation: more than 5 gadolinium-enhanced lesions or a tumefactive demyelinating lesion detectable by magnetic resonance imaging, the disease progressing to the point that additional treatment with methylprednisolone or plasma exchange was required, and progressive physical disability reflected by a 1-point or more increase in patients' scores on the Expanded Disability Status Scale, or EDSS, Thirty-one patients at the university’s MS clinic who had discontinued Gilenya were included in the study. Eight experienced SDR and 11 relapses. The mean time for SDR patients' reactivation to occur was 2.6 months, researchers said. Patients had significantly higher levels of lymphocytes — white blood cells involved in autoimmunity — than during Gilenya treatment. When the team compared the disease features of SDR and non-SDR patients, they found that SDR patients had significantly higher annualized relapse rates before starting Gilenya and lower EDSS scores. “A higher ARR [annualized relapse rate] is the major contributory factor toward development of SDR,” the researchers wrote. “Patients who had higher ARRs before fingolimod [Gilenya] treatment must be closely followed up both clinically and radiologically in terms of the early signs of severe reactivation,” they wrote. About 38 percent of the SDR patients failed to respond to steroid treatment. They received a plasma exchange, which led to moderate improvement in their condition. Based on this finding, the researchers suggested that “plasmapheresis [plasma exchange] must be considered in patients exhibiting steroid-refractory SDR.” "In conclusion, SDR may be observed within the first 3 months after cessation of fingolimod," the team wrote. "This may be explained by the rapid influx of lymphocytes into the CNS [central nervous system]. Patients with higher annualized relapse rates and lower Expanded Disability Status Scale scores before commencing fingolimod treatment were more likely to exhibit SDR."  

Non-Hispanic whites, especially females, are more likely to die from multiple sclerosis (MS) than any other racial group, though blacks tend to die earlier, concludes a study by researchers at the University of Southern California’s Keck School of Medicine. Their survey, “Multiple Sclerosis Mortality by Race/ Ethnicity, Age, Sex,…

The Invisible Disabilities Association (IDA) has created a video to raise awareness about the hardships of disabilities that are real but not readily evident to passersby, and often complicate life for people with multiple sclerosis (MS) and other disorders. The video, called “I Am Invisible No More,” features…

A global collaboration of researchers led by Belgium’s Flanders Institute for Biotechnology has determined the structure of the pro-inflammatory cytokine IL-23 and its receptor IL-23R, which could be potential targets for treating multiple sclerosis (MS) and other autoimmune diseases. Their study, “Structural Activation of Pro-inflammatory Human Cytokine…

CannaMD plans two medical marijuana clinics in the Orlando area to evaluate patients for entry in the Florida Medical Marijuana Use Registry. The first clinic opened Jan. 17 in the suburb of Dr. Phillips; the second will open Jan. 25 in the Lake County town of Mt. Dora. CannaMD is a statewide…

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…

Thrombin, a blood clotting factor, may be involved in the inflammatory processes of multiple sclerosis patients,  particularly those with relapsing-remitting form of the disease (RRMS), a study found. Higher levels of thrombin may also explain the increased risk of cardiovascular disease linked to MS. By measuring thrombin levels, it may…

A majority of relapsing-remitting multiple sclerosis (RRMS) patients at a Swedish clinic who initiated treatment with Tecfidera (dimethyl fumarate; DMF) either stopped or switched to another therapy within two years, a study reports. Researchers in the observational study were not able to determine exact reasons for discontinuation. But, they wrote,…

Mallinckrodt Pharmaceuticals is seeking 66 participants for a clinical trial to determine the safety and effectiveness of its injected therapy H.P. Acthar Gel as a treatment for acute relapses in people with relapsing-remitting multiple sclerosis (RRMS). MS relapses are flare-ups of central nervous system inflammation that damage the myelin coating that protects nerve cells. The damage disrupts the transmission of impulses between the cells, causing spikes in MS symptoms. For severe relapses that interfere with a person’s mobility, safety or ability to function, most neurologists recommend corticosteroid treatment administered intravenously or taken orally. Steroids can also be administered by injection of a gel under the skin. H.P. Acthar Gel is designed to provide extended release of steroids in the body. The trial will evaluate whether the gel is an effective treatment for RRMS patients who have been unable to recover from a relapse after receiving high-dose intravenous or oral steroids. Researchers will randomly assign participants to receive either H.P. Acthar Gel or a placebo, delivered by injection once a day for 14 days. Follow-up visits will be required at 14, 28 and 42 days. The study's main objective will be seeing whether patients' disability improves. Researchers will use a standard tool for measuring disability known as the Expanded Disability Status Scale.  Other objectives will include seeing how the therapy affects patients' fatigue, quality of life, workplace productivity, and use of healthcare resources. Participants must have a confirmed diagnosis of RRMS, be older than 18 years of age, and have experienced a relapse within 29 days of enrolling in the trial. For more information about enrollment criteria and how to participate in the trial, please contact Valerie Carvajal at (800) 556-3314 or by email at [email protected]. The National Multiple Sclerosis Society announced in an MS trial alert that Mallinckrodt will be  enrolling participants in Tucson; Fort Collins, Colo.; Tampa; Atlanta; Savannah, Ga.; Northbrook, Ill.; Fort Wayne, Ind.; Indianapolis; Kansas City, Kan.; New York; Cleveland; Dayton, Ohio; Dallas; Round Rock, Texas; San Antonio; Salt Lake City; Richmond, Va.; and Tacoma, Wash. Without clinical trial participation there is no way for patients to obtain new medicines or for scientists to ultimately find a cure for MS. The National MS Society encourages participation. It has developed a guide for patients who want to take part in studies called “Participating in Clinical Trials.” It covers the basics of participation, benefits versus risks, patient protection, costs and other important issues about trials.  

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 approved lymphoma therapy Rituxan (rituximab) has shown promise as a treatment for  multiple sclerosis. A new study indicates the Genentech treatment is effective and safe against neurological diseases like MS for up to seven years. The research, “Long-term safety of rituximab induced peripheral B-cell depletion in…

The European Commission has approved Roche’s Ocrevus (ocrelizumab) for both relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS) across the 28-member European Union. The commission’s move —  nearly 10 months after the U.S. Food and Drug Administration (FDA) approved Ocrevus in March 2017 — makes it the first approved PPMS…

Probiotics increased the punch of treatments that decrease the inflammation associated with multiple sclerosis, a study found. Using the supplements to add helpful bacteria to the gut may be a way to improve patients’  outcomes, researchers added. The team from Harvard University-affiliated Brigham and Women’s Hospital did not…

A $44,000 National Multiple Sclerosis Society grant will allow a researcher at the Kessler Foundation to advance her work on multiple sclerosis patients’ emotional processing challenges. Dr. Helen Genova, Kessler’s assistant director of neuropsychology and neuroscience research, has been studying cognitive dysfunction in people with various diseases, including MS. In addition to neurological problems,…

Atara Biotherapeutics has received a green light to enroll U.S. patients into a Phase 1 trial of ATA188 for progressive or relapsing-remitting multiple sclerosis (MS). The study was initially launched in Australia, but with the U.S. Food and Drug Administration (FDA) having cleared the company’s application, the trial…

United Greeneries plans to launch online retail sales of medical cannabis in February for Canadians covered by the Access to Cannabis for Medical Purposes Regulations — a program for which certain multiple sclerosis (MS) patients may be eligible. United Greeneries, a unit of Harvest One Cannabis, an umbrella…

Multiple sclerosis patients whose first treatment is Genentech's Rituxan (rituximab) stay on it longer than other disease-modifying drugs that patients start with, a Swedish study reports. When they stop taking Rituxan,  it usually isn't for lack of effectiveness or side effects...

A British board that recommends what treatments the National Health Service should cover has advised the system to use only Extavia (interferon beta 1b) as a treatment for MS patients who continue to have relapses. Cost was at the heart of the National Institute for Health and Care…

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…

American CryoStem has received a warning letter from the U.S. Food and Drug Administration (FDA) for marketing its adipose-derived stem cell product Atcell without required regulatory approval, and for "significant deviations" from manufacturing processes that potentially raise safety concerns. The company has 15 working days to respond to the concerns raised by the agency and detail how they will be corrected, or risk "enforcement actions," the FDA said in a Jan. 4 press release. Studies suggest that mesenchymal stem cells can be used to alleviate symptoms and possibly treat several degenerative disorders, including multiple sclerosis. Atcell is a therapy based on the ability of mesenchymal stem cells isolated from adipose tissue (fatty tissue) to transform into a subset of mature cells, which include adipose cells, bone cells, and cartilage cells. Although not approved for use, Atcell is being distributed directly to physicians to treat patients affected by several life-threatening diseases, including Parkinson’s disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis, the FDA said in its release. It is administered intravenously, intrathecally (injection or infusion into the central nervous system) or by aerosol inhalation. The product is designed to be used in the same individual (autologous use) the cells are collected from, an approach intended to reduce risk. The cells are extracted using the company’s proprietary Cellect collection system. They are then expanded in the laboratory using the company's ASCelerate SF-M serum free (animal-product free) media, providing compounds needed for the cells to survive and proliferate. Stem cells put through this process are  ready to be used as therapy or to be stored for future use. A recent FDA inspection found that Atcell’s manufacturing steps are not in line with current good manufacturing practice requirements. Specifically, the manipulation of the adipose tissue was more than "minimal," the FDA reported, changing "relevant characteristics" of the original tissue that could introduce contamination by microorganisms or product defects and represent a "risk of harm" to patients. Because of this manipulation, FDA review is required by law to ensure Atcell's safety and efficacy, the agency said. Evidence of an inadequately controlled manipulation environment, lack of control of components used in production, and insufficient and inadequately validated product testing were also reported. “The use of Atcell raises potential significant safety concerns, due in part to the fact that there is little basis on which to predict how the product will perform in a patient,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in the release. “In addition, this product may also cause harm to patients who may put their trust in an unproven therapy and make the decision to delay or discontinue medical treatments proven to be safe and effective,” Marks added. American CyroStem, based in New Jersey, did respond to observations raised by the FDA at the time of its inspection. But they were found inadequate to support Atcell’s marketing, and failed to acknowledge that FDA approval was required, either by filing a biological license or investigational new drug application. “As part of our comprehensive policy framework for the efficient development and regulation of cell-based regenerative medicine, we’re going to be stepping up enforcement activities against those who manufacture and market products in ways that put patients at risk,” said Scott Gottlieb, FDA commissioner. “We see great promise from the field of cell based regenerative medicine, but there are also novel risks,” Gottlieb added. Healthcare professionals and patients who have used Atcell are asked to report any adverse events related to the treatment using the FDA’s MedWatch Online Voluntary Reporting Form. Completed forms can be submitted online, or via fax to 1-800-FDA-0178.  

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 Phase 3 clinical trial evaluating AB Science’s masitinib as a treatment for progressive multiple sclerosis can continue without having to add patients, an independent review board has decided. The decision indicates that the therapy has been effective enough that its population base does not need to be expanded, the…

MMJ International Holdings is seeking a patent for a part-cannabinoid and part-non-cannabinoid treatment for multiple sclerosis and other diseases. The company said in a news release that it filed the patent request ahead of Phase 2 clinical trials of the formulation.  The therapy was developed by MMJ Bioscience, an affiliate of MMJ International…

Iranian researchers have identified another herpes virus that may increase the risk of a person developing multiple sclerosis. The team identified the human herpesvirus 6, or HHV6, as a potential risk factor for MS through a meta-analysis of several studies. They published their findings, “Relationship of Human…

Multiple Sclerosis News Today brought you daily coverage of important discoveries, treatment developments, clinical trials, and other events dealing with multiple sclerosis throughout 2017. We look forward to providing more news to MS patients, family members, and caregivers during 2018. As a reminder of what mattered most to you in…

The U.S. Food and Drug Administration (FDA) has updated a safety bulletin about gadolinium-based contrast agents (GBCAs), after studies raised new concerns about them. Doctors often use GBCAs to diagnose multiple sclerosis (MS), monitor disease activity and verify the effectiveness of MS therapies. Gadolinium is a metal ion, or electrically charged molecule, that…