research

Patients with primary progressive multiple sclerosis have more severe cognitive impairment than those with relapsing-remitting multiple sclerosis, according to a German study that analyzed published data on the topic. PPMS patients did especially poorly on verbal learning and verbal memory tests, said the study, which suggested that PPMS patients need disease management that specifically focuses on their cognitive difficulties, which do not necessarily correlate with the degree of overall disability. The study gathered data from 47 previously published studies in an attempt to analyze potential differences in cognitive performance between patients with RRMS and PPMS. These studies included 4,460 patients — 3,456 with RRMS and 1,004 with PPMS — and plenty of information about patient and disease features. This allowed researchers to perform a meta-analysis of pooled data from various studies, that is considered the highest level of scientific evidence. Researchers noted that PPMS patients performed worse on cognitive tests, both when considering global scores and tests of specific cognitive domains. Yet both groups scored similarly in levels of anxiety, depression and fatigue. Using statistical analyses, the research team found that differences in sex, education, disease duration, manual dexterity and fatigue could not explain the poorer test results among PPMS patients. On the other hand, PPMS patients were, on average, older than those with relapsing disease, and the team found that this difference accounted for poorer test results in cognitive tests of processing speed and working memory. Yet differences in other cognitive aspects also remained when researchers took age into account. Differences in disability, measured by the Expanded Disability Status Scale, could also not explain why PPMS patients performed worse on the cognitive tests. A detailed look revealed that the largest differences between RRMS and PPMS patients were in verbal learning and verbal memory, along with the age-associated difference in processing speed. Depression and anxiety also brought down processing speed, researchers said, even though the two groups did not differ in their levels of anxiety and depression. The data shows that cognitive impairment in MS is not directly related to the course of the disease. Research may explain differences in other factors including genetics, the degree of brain tissue loss and medications.

Having a concussion when you’re 11 to 20 years old could increase your risk of developing multiple sclerosis later, a Swedish study suggests. The collaboration between Örebro University and Karolinska Institutet showed that a concussion in adolescence raised the risk of developing MS by 22 percent. Two or more concussions…

Autologous hematopoietic stem cell transplants for relapsing-remitting multiple sclerosis (RRMS) are superior to currently approved disease-modifying drugs, according to a Swedish study published in the Journal of Neurology, Neurosurgery & Psychiatry. In addition, says the review, the procedure’s safety profile has improved in the last decade, and is now just…

Older Women with MS Age Better Than Their Male Counterparts, Canadian Survey Finds I have to say that, as a 69 year old man with MS, this report is a bit depressing. In fact, one of its findings is that older men are depressed while older women…

Structural changes of the eye retina are a common feature among multiple sclerosis patients with a clinical history of optic neuritis, a Danish study finds. Loss of the myelin protective layer of optic nerve cells due to inflammation causes optic neuritis. About 20 percent of MS have it, and optic neuritis is a symptom of disease progression in about 40 percent of patients. In most cases, symptoms persist, leading to visual impairment or blindness, along with pain. Non-invasive optical coherence tomography can help evaluate neurodegeneration of optic nerve cells. This imaging technique allows a three-dimensional evaluation of internal eye structures, including the thickness of the retina nerve fiber layer. Previous studies have shown that MS patients may present progressive RNFL loss, but this can also be caused by optic neuritis. The use of OCT has been proposed to distinguish MS subtypes and evaluate disease activity. However, little clinical data is available to validate OCT's accuracy and potential as a diagnostic tool. To find out more, a Danish research team conducted a long-term evaluation of structural and functional visual outcomes in MS patients with and without a history of optic neuritis. Researchers observed that patients with a history of optic neuritis had significantly more RNFL thickness loss than those without optic neuritis. They linked reduced RNFL thickness with a 1.56 times higher risk of optic neuritis development. Nevertheless, the team did not find any association between optic neuritis and functional impairment of visual acuity or color vision. Use of high-resolution OCT devices coupled with up-do-date analysis software can improve the diagnostic efficacy of this imaging technique in MS patients, said researchers, who urged more studies to address the relevance of structural changes in MS.

University of Southern California researchers are recruiting 400 Hispanics who have been diagnosed with multiple sclerosis in the past two years for a study about genetics’ and cultural perceptions’ effect on the severity of the disease. More specifically, the Keck School of Medicine team will look at whether the stressful process of…

Two researchers at the University of Tasmania’s Menzies Institute for Medical Research have received an innovative multiple sclerosis research fellowship that was created to drive basic scientific research into treatment development and the doctor's office. MS Research Australia and The Macquarie Group Foundation founded the three-year, $750,000 program. It is unique in that it will bring together basic science researchers and therapy-development researchers to try to convert laboratory research into disease solutions. The grant was awarded to Professor Bruce Taylor, a Menzies researcher who is also a neurologist at the Royal Hobart Hospital, and to Dr. Kaylene Young, a neuroscientist whose long career in laboratory research has focused on mechanisms that the brain uses to repair itself. Taylor’s achievements include identifying genetic mutations that may increase the risk of a person developing MS. The award will help him move these discoveries to the lab to determine how the mutations harm cells. Young discovered that a type of non-invasive brain stimulation can increase brain stem cells' ability to produce new cells that repair the nervous system. She plans to move the technology, known as transcranial magnetic stimulation, from the lab to therapy-development-related research.

Three-fourths of relapsing multiple sclerosis patients who took two short courses of Mavenclad over two years remained relapse-free for four years, according to newly published data from the medication's Phase 3 extension trial. Moreover, patients who took Mavenclad during the first two years and then a placebo for the next two years fared similarly to those who took Mavenclad for the entire four-year period. The European Commission on Aug. 25 approved Mavenclad — developed by Merck KGaA (known as EMD in North America) — to treat relapsing forms of MS in Europe. It based that approval on data from the Phase 3 CLARITY, CLARITY EXTENSION, and ORACLE-MS trials, as well as the Phase 2 ONWARD trial, and the ongoing long-term PREMIERE study. Besides showing the long-term impact of two short courses of Mavenclad — patients took tablets for a maximum of 20 days over two years — this latest study showed that continuing treatment into the third or fourth year offered no additional benefits. This finding supports Merck’s earlier studies, which suggested that Mavenclad resets the immune system. This is a stark contrast in treatment approach to most approved MS drugs which work by suppressing either T- or B- immune cells over the long term. Researchers also deemed safety to be similar in the two groups. Most adverse events were mild or moderate, and most patients who had their B-cells and T-cells depleted in the first part of the study had normal, or nearly normal, levels at the end of the extension. Shingles were most common in patients who received the highest cumulative dose of the drug, affecting 4.8 percent of participants. But in the remaining treatment groups, rates of the viral infection were similar at 1.1 to 2 percent, researchers said. Besides Merck's own studies, an independent study recently demonstrated that Mavenclad also improves patients’ quality of life. As such, the company plans to file regulatory approval for Mavenclad in the United States and elsewhere.

Gilenya decreased relapses in children and adolescents with multiple sclerosis in the phase 3 PARADIGMS trial, according to the therapy's developer, Novartis. The Swiss company will present the trial's results at the 7th Joint ECTRIMS-ACTRIMS meeting, set for Oct. 25-28 in Paris. The study addressed the safety and efficacy of an oral, once-daily dose of Gilenya in 215 MS patients aged 10 to 17. Participants received 0.5 mg or 0.25 mg of Gilenya, according to their body weight, and results were compared with those of intramuscular Avonex (interferon beta-1a given once weekly). The trial — conducted at 87 sites in 25 countries — was designed in partnership with the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the International Pediatric Multiple Sclerosis Study Group. Gilenya led to a "clinically meaningful decrease in the number of relapses" over a period of up to two years, compared to Avonex, according to the trial. The safety results of Gilenya matched those observed in previous trials, with adverse events more likely among the Avonex group. Importantly, the PARADIGMS trial is the first-ever randomized, controlled Phase 3 study of a disease-modifying therapy in pediatric MS. No treatment is currently available for children and adolescents with MS. Novartis will now complete a thorough evaluation of the results and later submit Gilenya for approval by regulatory agencies. It will also extend the study to a five-year period.

Older men with multiple sclerosis (MS) have more harmful lifestyles than older women with the disease, concludes the Canadian Survey of Health, Lifestyle and Aging with Multiple Sclerosis. Treatment for depression could go a long way to promoting more healthy lifestyles for all older MS patients, authors suggest. The study, “…

TG Therapeutics will discuss ublituximab's ability to deplete B-cells linked to multiple sclerosis and to reduce inflammatory brain lesions at the 7th Joint ECTRIMS–ACTRIMS Meeting in Paris next month. The three presentations will cover preliminary results of a Phase 2 clinical trial of ublituximab's safety and effectiveness as a treatment for relapsing forms of MS, the company said in a press release. The conference will be Oct. 25-28. Dr. Amy E. Lovett-Racke of Ohio State University will discuss ublituximab's ability to decrease B-cells associated with MS after six months of treatment. Ublituximab is an antibody that targets B-cells carrying the CD20 protein on their cell surfaces. These cells are thought to play a role in MS development. Dr. Matilde Inglese of the Icahn School of Medicine at Mount Sinai in New York will discuss ublituximab's ability to decrease study participants' inflammatory brain lesions. And Dr. Edward Fox of Central Texas Neurology Consultants, the trial's principal investigator, will do a poster-session presentation on the study's patient characteristics and preliminary results as a whole, including safety. The ongoing Phase 2 trial is still recruiting patients with relapsing forms of MS. Researchers are randomly assigning participants to receive intravenous infusions of either ublituximab or a placebo. One of the study’s primary goals is to see how well ublituximab depletes B-cells 28 days after the start of treatment. Another primary goal is to see how safe the therapy is, with the measurement being treatment-related adverse events that patients experience over six months. Ublituximab’s ability to reduce relapses will be a secondary measure of the trial. Researchers will assess it after 48 weeks of treatment. Fox, who is the director of the Multiple Sclerosis Clinic of Central Texas, and a clinical assistant professor at the University of Texas Medical Branch in Round Rock, made a ublituximab presentation at the 3rd Congress of the European Academy of Neurology in June. It revealed that the therapy nearly depleted B-cells only four weeks after treatment started. Earlier data suggests that ublituximab can be administered in only one hour. Ocrevus, the only approved MS therapy that targets B-cells with CD20, requires 3 1/2 hours. Although the Phase 2 trial is continuing, the data generated so far supports plans for two Phase 3 trials, TG Therapeutics said. They will randomize patients to receive either ublituximab or Aubagio. The trials, which the company hopes to start by the end of September, will be conducted under a Special Protocol Assessment agreement with the U.S. Food and Drug Administration. It allows the FDA to evaluate the design and population size of a trial a company intends to use to seek a drug's regulatory approval. The FDA has refused to approve therapies whose trial design it believed to be flawed. Obtaining a design sign-off before a trial improves the chance of a treatment being approved if it meets the study's objectives.

You’ve just “biked for MS” or your friends have just “walked for MS” and they’ve collected a lot of pledges. Maybe you sent out letters to your friends asking them to donate a little cash to help find a cure for this disease that has impacted our lives.

Past infection with the Epstein-Barr virus (EBV) has been reported to increase the risk for multiple sclerosis (MS). Now, researchers have found a link between EBV and MS in three racial-ethnic groups, with African-Americans and Latinos showing a higher risk for MS than Caucasians.

Tecfidera (dimethyl fumarate) can be a suitable replacement therapy when Tysabri (natalizumab) is discontinued, keeping low levels of disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), according to a report published in the Journal of Neurology, Neurosurgery & Psychiatry. Several studies have demonstrated the effectiveness and…

Striking similarities between patients with multiple sclerosis and a type of schizophrenia suggest the disorders are related, according to a review of a number of studies. Dr. Boris M. Arneth wrote the article, “Multiple Sclerosis and Schizophrenia.” It was published in the International Journal of Molecular Sciences. MS…

A Phase 2b trial assessing the experimental retroviral-targeting treatment GNbAC1 in patients with relapsing-remitting multiple sclerosis (RRMS) failed to meet its primary goal of reducing brain lesions and other signs of brain inflammation within six months. But researchers at GeNeuro and Servier — the two European companies that jointly developed the drug…

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…

Horseback Riding Plus Standard Care Can Help MS Patients Improve Balance, Other Symptoms Absolutely, it can. I don’t need to read this study to know that because I’ve been there, done that. About five years ago, at 64, I got back on a horse for the first…

Beth Kantor, 42, now knows what it really means to get down in the dirt. For the past four years, she’s volunteered as a first-aid assistant at the annual Twin Cities MuckFest, a fundraising event that the National Multiple Sclerosis Society organized in suburban Minneapolis. But this year, Kantor decided it…

Alkermes is funding a Phase 3 clinical trial evaluating the effects of its ALKS 8700 therapy on the gastrointestinal tracts of relapsing-remitting multiple sclerosis (RRMS) patients, compared to Tecfidera (dimethyl fumarate), according to a news release by the National Multiple Sclerosis Society. ALKS 8700, an orally administrated form of monomethyl fumarate, is still…

I’ve just added an app to my iPhone that’s designed to track how I’m doing day-to-day with my MS. Not only can the data it collects be useful to me and to researchers, the app also is fun to use. The app is called elevateMS. It’s…

Omega-3 fatty acids might reduce inflammatory processes by boosting a mechanism that cleans out dysfunctional or unnecessary proteins in a certain type of immune cells, according to a study published in the journal Autophagy. These insights indicate that omega-3 supplements might be beneficial for certain multiple sclerosis (MS) patients,…

Topas Therapeutics and Eli Lilly and Company are teaming up to develop compounds that could be used to treat inflammatory and autoimmune diseases, such as multiple sclerosis and diabetes. The compounds, based on a Topas technology platform, will be aimed at restoring immune tolerance. Immune tolerance refers to the immune system being unresponsive to certain antigens — for instance, the body’s own proteins. Without immune tolerance, the body can generate an excessive immune response that prompts the immune system to attack healthy organs or tissue — a process called autoimmunity Under the multiyear agreement, Topas will receive research and development funding. It will also receive financial rewards from the success of any drug developed under the collaboration. The agreement will give Lilly the option to license all therapies created under the collaboration, and to develop them further. "We are excited to be working with Lilly to generate drug candidates using our proprietary technology," Timm Jessen, the CEO of Topas Therapeutics, said in a press release. "We expect this work to support the value of our approach" of triggering immune tolerance against antigens, he said. The fact that an important pharmaceutical company like Lilly is interested "in our technology, we believe, supports the strong commercial potential of our work." Topas develops compounds against autoimmune reactions — that is, situations in which the immune system attacks healthy parts of the body. It is already developing treatments for multiple sclerosis, type 1 diabetes, celiac disease, and other autoimmune disorders. While the majority of such therapies try to shut down the immune system, Topas’ approach is to trigger antigen-specific immune tolerance. This allows the body to regain control over an excessive immune response, while sparing the body's normal immunity. Topas links its compounds to tiny nanoparticles that liver sinusoidal endothelial cells can absorb. The liver cells are the first place where immune T-cells can learn what the body should not fight against. In studies of mice with multiple sclerosis, a single injection of nanoparticles containing peptides found in neurons triggered a potent protective effect, improving the disease's symptoms and blocking its progression. Peptides are components of proteins. "Lilly is committed to be an innovation leader in immunology," said Dr. Thomas F. Bumol, senior vice president of biotechnology and immunology research at Lilly. "Topas has a very novel approach to immune tolerance induction, which we would like to see successfully applied to certain disease-relevant antigens. We look forward to working together with Topas on their unique platform."

A multiple sclerosis study will collect information about patients' movement performance and symptoms from their smartphones, Novartis has reported. The study is aimed at evaluating in real time the daily challenges of people living with MS. The results may help researchers develop new ways to measure treatments' effectiveness, the company said. Novartis is partnering on what it has dubbed the elevateMS study with Sage Bionetworks. The non-profit research organization is developing new predictors of disease to accelerate health research. A cellphone application will allow MS patients to send information about their situation from anywhere. The app will use sensors to gather information on patients' movements. It will also assess functional performance tasks that participants engage in. Patients can also fill out questionnaires with the app. A division of Apple called the Apple ResearchKit platform developed the app. Those interested in participating in the study can download it here. The elevateMS app allows a smartphone user to register important features of their disease. It includes a symptom tracker tool that allows users to record their overall wellness. They can also get an overview of what's been happening to them on an activity dashboard. Patients, neurologists and disease advocates gave Apple's app team input that helped with the design. "As physicians, we always want to know how our patients with MS are doing on the treatments we prescribe," Dr. Stanley Cohan, medical director of the Providence Multiple Sclerosis Center in Portland, Oregon, said in a press release. "With the elevateMS app, study participants can frequently document their symptoms in a personal health story," said Cohan, one of the scientific advisors to the study. "In turn, this data may provide researchers with new ways to look at disease progression and treatment effectiveness." The elevateMS study is open to MS patients 18 years old or older in the United States who own a smartphone. Additional information about it is available at www.elevatems.org.

Nortis, a Seattle-based biotech company, has received a $688,000 grant by the National Institutes of Health to create a living, 3-D model of the human blood-brain barrier that will be used for laboratory testing to accelerate drug development and lessen the likelihood of failure in clinical trials. This grant provides funding for a third year of a Small Business Innovation Research (SBIR) award given to Nortis by the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the NIH. SBIR provides grants to U.S.-based small businesses to do federal research and enable the commercialization of technology. The blood-brain barrier is a tissue barrier that only allows certain molecules to pass from blood vessels into the brain. It is a protective mechanism to prevent the entry of foreign bodies and infection-causing organisms in the brain. Researchers are trying to find ways of delivering medications across this barrier, to reach brain tissues to treat diseases that include multiple sclerosis. "Understanding how drugs are transported across the blood-brain barrier and interact with the brain presents a significant scientific challenge," Thomas Neumann, CEO of Nortis and principal investigator on the project, said in a press release. "More predictive preclinical models based on human tissue are urgently needed to reduce costs and minimize clinical trial failures," he added. "This grant will help us develop new in-vitro alternatives to traditional pharmaceutical drug development testing on laboratory animals."

Chronic stress and inflammation in the brain can cause multi-organ dysfunction including severe gut failure, mediated by a newly identified nerve pathway in animal models of multiple sclerosis, a Japanese study shows. MS is an autoimmune disease caused by CD4+ T-cells that cross the blood-brain barrier protecting the central nervous system. This inflames and stresses the brain and spinal cord. In previous studies, a team led by professor Masaaki Murakami of Japan's Hokkaido University showed that these cells could cross the blood-brain barrier in specific sites. These entrance sites depend on brain regional activation, which was found to be triggered by specific nerve interactions — a mechanism the team called gateway reflexes. In collaboration with other Japanese researchers and a team from Germany, the project aimed to address the potential correlation among chronic stress, brain inflammation and organ failures in MS. Using mice with MS-like disease — the experimental autoimmune encephalomyelitis model — researchers found that animals that had autoreactive CD4+ T-cells and which were exposed to stressful conditions developed severe symptoms such as gastrointestinal failure, or even death. Detailed analysis of the animals' brains showed that in stressed mice, CD4+ T-cells accumulated in two specific sites in the center of the brain around blood vessels. This event would cause inflammation around those vessels, and activation of a nerve pathway that is commonly turned off. This switch led to gut dysfunction, bleeding and failure. "These results demonstrate a direct link between brain micro-inflammation and fatal gastrointestinal diseases via the establishment of a new neural pathway under stress," Murakami, the study's senior author, said in a news release. Researchers were able to prevent gut symptoms by inhibiting inflammation in the brain or blocking the nerve pathway responsible for driving the signals from the brain to the gastrointestinal tract. "Micro-inflammation in the brain is also seen in Alzheimer's disease and Parkinson's disease," Murakamai concluded. "So it's of particular interest to investigate possible connections between brain micro-inflammations and organ dysfunctions, including those within the brain itself, in those patients."

Brain donation for multiple sclerosis research optimizes the chances that a cure might be discovered. It might result in a vaccine or other preemptive strike to prevent the disability from starting in the first place. As addressed in a previous column, there is a shortage…

A new and potentially important mechanism in the development of autoimmune diseases like multiple sclerosis was discovered by scientists at the University of Freiburg, Germany. They identify a protein, called Caveolin-1, that is essential to immune cells called B-cells working as intended to protect a person from pathogens or — in its absence…

Older Immunosuppressants May Increase MS Patients’ Cancer Risk, Study Reports We’re talking about some pretty harsh immunosuppressant drugs here: azathioprine, mitoxantrone, and possibly cyclophosphamide. Unlike newer drugs, targeted to specific cells, these knocked out an entire spectrum of immune cells when they were administered. If you’ve used…

British military personnel are at significantly higher risk of dying from multiple sclerosis than people in other occupations, a study reports. University of Southampton researchers had done a previous study of mortality rates by occupation by checking records of residents of England and Wales. They noticed that the death rate among MS patients in the armed forces was much higher than that of people in other professions over three successive decades. MS has a genetic component but is also influenced by environmental factors, including vitamin D deficiency, smoking and certain viruses. Researchers wanted to learn why so many military people die of MS, and the causes. The team looked at the death records of men aged 20-74 between 1979 and 2010. They compared military people's MS-related mortality rates and death rates from all motor neuron diseases with those of other occupations. They also compared rates across social classes, which in the military presumably means lower-ranking enlisted people, higher-ranking enlisted people, and officers. They discovered that the MS-related mortality rate among military people was significantly higher than in other professions. The death rate from MS was also significantly higher than the rate from all motor neuron diseases in the armed forces. Interestingly, military people did not have a higher MS-related death rate when the team divided those in the study into three social classes or when they compared the armed forces mortality rate to those of similar occupations, such as police and fire services. The consistency of the findings, together with the high statistical significance observed, indicated that the results were not due to simple chance or a problem with the study method, the team said. They speculated that the higher military death rate could stem from the close proximity in which military personnel live and work, which could facilitate the transmission of infections that have the potential to cause MS. The results conflicted with those of a study that analyzed hospital admissions due to MS in a population of former military personnel. It reported no increased incidence of MS-related admissions in former military people, compared with non-military controls. Since such cohort studies are less prone to bias, the Southampton team called for more research on the topic.