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A new study draws a reverse link between the number of MRI scans of multiple sclerosis patients who are on interferon-beta 1a and doctors declaring there is evidence of the patients’ disease worsening. When doctors looked at one scan, rather than multiple ones, they were more likely to say that…

According to a study by researchers at Cleveland's Case Western Reserve University School of Medicine, pre-existing inflammatory diseases affecting the central nervous system make mesenchymal stem cells less effective in treating multiple sclerosis. The study notes that MSCs potentially produce several signaling proteins that can regulate immune system responses as well as help tissue regenerate. Preclinical studies have shown that this can reduce brain inflammation while improving neural repair in animal models of experimental autoimmune encephalomyelitis -- an animal version of MS that is often used in laboratory studies, since it resembles the inflammation and neuronal damage seen in MS patients. Given the need for effective new MS therapies, the results will help MSCs to advance to human clinical trials. So far, results have reported good safety data, though such therapies have failed to demonstrate therapeutic efficacy. Most such trials so far have used stem cells collected from the patient, a process known as autologous transplantation — yet this may explain why MSCs have not been effective. It's possible that pre-existing neurological conditions may alter stem cells' responsiveness as well as their therapeutic activity. To see whether that is in fact the case, team members collected stem cells from the bone marrow of EAE mice. But these stem cells were unable to improve EAE symptoms, whereas stem cells collected from healthy mice retained all their therapeutic potential and improved EAE symptoms. A more detailed analysis showed that the MSCs derived from EAE animals had different features than their healthy counterparts. In addition, the team confirmed that MSCs collected from MS patients were also less effective in treating EAE animals, compared to MSCs from healthy controls. Indeed, these MSCs from patients produced pro-inflammatory signals instead of the protective anti-inflammatory ones. “Diseases like EAE and MS diminish the therapeutic functionality of bone marrow MSCs, prompting re- evaluation about the ongoing use of autologous MSCs as a treatment for MS,” the team wrote, adding that its study supports the advancement of MSC therapy from donors rather than autologous MSC therapy to treat MS while raising "important concerns over the efficacy of using autologous bone marrow MSCs in clinical trials."

Christine Sinclair, captain of Canadian women’s soccer teams that won two Olympic bronze medals, has joined the fight against multiple sclerosis by supporting A&W’s Burgers to Beat MS campaign. The Multiple Sclerosis Society of Canada said Sinclair will visit A&W restaurants across Canada on Aug. 23 and 24 to raise funds and awareness of MS. Sinclair is close to the cause because her mother, Sandi, who coached her soccer teams when Christine was a child, has the disease. Sandi is one of about 100,000 people with MS in Canada, which has the highest rate of the disease in the world. "I have become a part of this to educate the public and support finding a cure," Sinclair said in a press release. "I don't want other people to go through what my family has gone through, with the difficulties my mom faces every day." Sandi Sinclair now lives in a long-term care facility. Christine decided to help the MS Society of Canada after her mother's mobility become more and more limited, and she finally ended up in a wheelchair. "Each year we look forward to our partnership with A&W," said Valerie Hussey, chair of the MS Society of Canada's board of directors. "We are excited to have Christine, a Canadian icon, share her personal connection to MS and help raise awareness for our cause." Burgers to Beat MS, now in its ninth year, has raised nearly $10 million for the cause. It is the country's largest annual fundraiser benefiting the MS Society of Canada. From this week on, about 900 A&W restaurants nationwide will be helping the society raise funds. Supporters will be able to donate by rounding up their bill at the register, by buying $1, $2 or $5 paper cutouts, or by dropping cash in donation mugs. Supporters will also be able to contribute online. The campaign will end with a special day on Thursday, Aug. 24, when those who run the restaurants double every donation made from the sale of Teen Burgers. This means the donation on each burger will go from $1 to $2.

A new study reports that vitamin D supplements do not prevent bone loss in multiple sclerosis patients who are not vitamin-D-deficient. Previous research has suggested that low levels of vitamin D increase the risk of a person developing MS. In addition, Vitamin D prevents loss of bone density. That loss can lead to fractures and osteoporosis, a condition that many MS patients experience as their disease progresses. Researchers decided to investigate the effect of weekly doses of vitamin D3 on patients with relapsing-remitting multiple sclerosis, versus patients receiving a placebo. All 68 participants in the Phase 4 clinical trial also received 500 mg a day of calcium, a compound that is also important for bone health. The team measured the effectiveness of the supplemental vitamin D by analyzing biomarkers of bone health in blood. These included levels of the proteins PINP, or procollagen type I N propeptide, and CTX1, or C-terminal cross-linking telopeptide. At the start of the study, levels of PINP and CTX1 were not significantly different between the two groups. And that continued to be true at week 48 and week 96 of the study. The bottom line was that vitamin D supplementation did not change bone health in patients with MS after 96 weeks. “Our results do not support that high dose weekly vitamin D supplementation is beneficial for bone health in ambulatory persons with MS, and suggest that weekly vitamin D supplementation alone is not sufficient to prevent bone loss in persons with MS who are not vitamin D deficient,” the researchers concluded. The results were different from previous studies supporting the beneficial effects of vitamin D supplementation in MS patients. The researchers said they believed the discrepancy was due to differences in the studies' patient characteristics, sample size, and duration of follow-up.

Ocrevus' market introduction is off to a stellar start, with nearly half of neurologists surveyed by Spherix Global Insights saying they are using the therapy — the first ever approved for both relapsing and primary progressive multiple sclerosis. Within six months, 80 percent of neurologists are expected to prescribe Ocrevus, according to a report in the second-quarter edition of RealTime Dynamix: Multiple Sclerosis by Spherix Global Insights. But insurance is having an increasing impact on treatment decisions, the report also found, according to a Spherix press release. More patients are receiving less than optimal care because of inadequate or inferior insurance coverage, and neurologists report that insurers have become more aggressive in managing MS patients. Surveying 104 neurologists in June, the report showed that physicians followed through with their intent — reported in earlier surveys — to prescribe Ocrevus as it became available. With Ocrevus being the first approved drug for primary progressive MS, these patients make up a sizable part of those receiving it. But patients with relapsing forms of MS represent more than half of new users, according to the report. Ocrevus was also, by far, the drug that neurologists had learned most about, and felt most excited about using, the report added. Most of the patients on Ocrevus were switched from Biogen's Tysabri or Rituxan — a drug that, like Ocrevus, is also produced by Genentech/Roche. One in five patients was switched from an oral disease-modifying treatment, mainly Biogen’s Tecfidera (dimethyl fumarate). But for about 25 percent of Ocrevus-treated patients, the drug is the first disease-modifying therapy they have received. The survey also revealed that patients are the driving force behind new Ocrevus prescriptions. Seventy-one percent of neurologists receive requests from patients who want to start the treatment. While neurologists have to turn some of these requests down for various reasons, a large proportion of those who ask for the treatment receive it. Another insight from Spherix’s “RealWorld Dynamix: DMT Brand Switching in MS” survey was that patients' requests for a specific brand are often honored. Seventy-seven percent were prescribed the brand they requested, the survey showed. Interestingly, neurologists believed the number to be lower. Most patients who made a specific request, the report indicated, asked for Tecfidera in the past year and a half. Tecfidera is by far the leading oral disease-modifying drug prescribed in MS. Meanwhile, according to the report, Biogen's Avonex, Bayer's Betaseron, Teva's Copaxone, and EMD Serono's Rebif continue on a downward path. At least 30 percent of neurologists report lower use of these therapies in the past three months. Patients previously on these drugs are mainly switched to oral disease-modifying drugs. But this trend is projected to slow, with only Sanofi-Genzyme's oral Aubagio (teriflunomide) continuing to grow. But the choice of treatment may increasingly be driven by insurance. Compared with the same quarter of 2016 — when neurologists estimated that 14 percent of patients received suboptimal treatment because of poor insurance coverage — 20 percent of patients are now judged to be in this situation. Also, 60 percent of surveyed physicians feel that insurance companies have become more aggressive in MS treatment management. A similar percentage also say that insurance policies influence how they prescribe specific disease-modifying drugs.

Fatigue, limited mobility, and poor self-esteem or resiliency were found to be associated with periods of serious depression among multiple sclerosis patients, according to a recent study. Previous research has suggested that MS patients are at risk of major depression, with potentially profound impact on their quality of life. But only a few studies have addressed the incidence of depression among MS patients or the risk factors that may underlie its occurrence. Researchers in Canada enrolled 188 MS patients being treated an Alberta clinic, who were interviewed to assess potential risk factors for depression: namely, socioeconomic status, disease-related factors, childhood risk factors, psychosocial factors, and health behaviors. Participants were also asked to complete the Patient Health Questionnaire every two weeks for six months to identify depressive symptoms in real-time. Over a six-month follow-up, 36 cases of depression were reported among the group of MS patients analyzed. The incidence of depression was 0.019 for women, but higher — 0.044 — for men. Importantly, several factors seemed to be associated with depression in these patients — fatigue, limited mobility, and low resiliency, self-esteem, and self-efficacy, as well as poor coping skills. Results also showed that gender and income were associated with depression. Overall, the researchers concluded that "depression in MS exhibits a risk factor profile similar to that of depression in the general population, with the additional impact of MS illness-related factors. Potentially modifiable risk factors, such as coping with stress and resiliency, present opportunities for focus of further research in depression in MS treatment and prevention efforts." Concerning treatment, the team also emphasized that "while there is evidence in the clinical context that supports the efficacy for pharmacologic and non-pharmacologic treatments for depression in the general population, there is currently insufficient evidence to support/or refute the efficacy of depression treatment for individuals with MS ... Clearly this is an area that requires additional research."

Costs associated with multiple sclerosis increase as the disease worsens, according to a study of more than 16,000 patients in 16 European countries. The study, “New insights into the burden and costs of multiple sclerosis in Europe,” was published in the Multiple Sclerosis Journal. Researchers obtained their information from patient self-reporting. Patients used the Kurtzke's Expanded Disability Status Scale (EDSS) to assess the severity of their disease. They also reported on their quality of life and their resource use. Patients were divided into three categories. Those with a score between 0 and 3 on the EDSS scale were deemed to have a mild disease. The disease of those with scores of 4 to 6.5 was considered moderate. And the disease of those with scores of 7 to 9 was classified as severe. Patients assessed their health-related quality of life with the EuroQol Five Dimensions questionnaire. The average age of the 16,808 participants was 51 and a half years old. The work capacity of MS patients dropped from 82 percent of a healthy person's to 8 percent as the severity of the disease increased, researchers said. Patients' quality of life scores were about the same as those seen in the general population when they had a mild disease. But they plunged to less than zero when their disease became severe. The mean annual cost of having a mild form of MS was 22,800 euros, or around $26,300, researchers reported. The cost of having a moderate disease was 37,100 euros, or about $42,800. And the cost of a severe disease was 57,500 euros, or $66,340. Healthcare accounted for 68 percent of total costs with a mild disease, 47 percent with a moderate disease, and 26 percent for a severe disease. "Costs are dependent on the availability, use and price of services and on disease severity," the researchers wrote. "Costs were related to disease severity" in all countries "and were dominated by production losses, non-healthcare costs and DMTs," or disease-modifying therapies. Those therapies may be a key reason why the highest percentage of healthcare costs occurred in patients with a mild disease, researchers said. Doctors prescribe a lot of DMTs to this group. Other factors related to the high percentage were that many patients with mild diseases are still able to work -- meaning they incur fewer production-loss costs -- and this group requires fewer community services. As MS becomes more severe, patients' production losses rise, and they use more community services. "The intensity of healthcare service use varied widely across the countries," researchers wrote. "This reflects differences in healthcare organization, medical traditions, ease of access and – most importantly – availability of given services." Researchers also assessed patients' levels of fatigue and cognitive difficulties. Ninety-five percent reported fatigue, and 71 percent cognitive difficulties. Fatigue and cognitive difficulties had significant impacts on quality of life scores, researchers said.

GeneFo, an online multiple sclerosis (MS) community that offers support, advice and educational resources to patients, will conduct a free webinar July 26 for those interested in knowing more about how MS affects sex and intimacy. The webinar, hosted by renowned MS expert Dr. Tuppy Owens, follows a GeneFo survey showing that sex…

Australia has become the first country to approve Genentech's Ocrevus for relapsing and primary progressive multiple sclerosis treatment since the therapy's initial approval by the U.S. Food and Drug Administration in March 2017. The Australian Therapeutic Goods Administration gave Ocrevus the green light on July 17, filling an unmet need for Australia's estimated 23,000 MS patients. “We are pleased that another regulatory body recognized for its rigorous review process has approved Ocrevus with a broad label as a new treatment option for people with relapsing or primary progressive MS in Australia,” Dr. Sandra Horning, Roche’s chief medical officer and head of global product cevelopment, said in a press release. “Approval in Australia is significant because of the high prevalence of MS in the country, making it the leading cause of non-traumatic disability in young adults." The drug's developer, Genentech, and Genentech's parent company Roche have submitted applications to get Ocrevus approved in more than 50 countries in Europe, Latin America and the Middle East. Ocrevus trials showed that, among relapsing patients, relapse rates were nearly halved compared to those treated with Rebif. Many of these patients also reached a level of no disease activity — measures that Genentech has continued to explore after the drug's U.S. approval. In addition, data also showed that PPMS patients, who deteriorate more rapidly, benefit from Ocrevus treatment. “People with PPMS [primary progressive multiple sclerosis], who often experience faster and more severe disability, have not had any approved treatment until Ocrevus," Horning said. "We continue to work closely with regulatory authorities across the world to bring Ocrevus to people with multiple sclerosis as soon as possible." Ocrevus is an antibody that blocks the CD20 molecule on certain immune B-cells. Researchers believe these cells directly damage myelin — the protective coat that insulates nerve cells in the brain and spinal cord. Evidence also indicates that B-cells can directly damage neurons themselves. The drug continues to be evaluated in a range of clinical trials, including one that specifically focuses on how the drug’s B-cell depleting actions play out to harness MS disease processes.

A recent patient survey reveals that almost one in four people with multiple sclerosis in the U.K. are not aware of available treatments that could help delay the onset of disability, even though a clear majority put disability as a chief worry. The report, funded by Sanofi Genzyme, was conducted by Adelphi…

In a pilot study with patients with multiple sclerosis, high-intensity interval training combined with resistance training improved physical capacity and quality of life in a pilot study of multiple sclerosis (MS) patients — whether or not they were disabled. French researchers at the University of Strasbourg assessed physical capacity, strength and quality of life before the training started, and then again after completing a 12-week exercise program. They divided participants into two groups: one of 18 patients with no disabilities, and a group of eight with disabilities. Participants followed a personalized exercise program involving both high-intensity interval training — a kind of cardiovascular exercise strategy alternating short periods of intense anaerobic exercise with less intense recovery periods — and resistance training to improve muscular strength and endurance. Scientists used a French version of the Multiple Sclerosis Quality Of Life-54 test — a questionnaire filled out by MS patients to measure health-related quality of life — with five additional questions. After the exercise program, women improved significantly in vitality, general well-being and physical health composite scores in the quality of life assessment, while men showed no significant improvements. Vitality and general well-being only improved in the group with no disability. Peak oxygen consumption improved by 13.5 percent, and maximum tolerated power — a measure of maximum energy that can be expended — by 9.4 percent. Muscle strength increased in both quadriceps and hamstrings. Women showed better improvements than men in peak oxygen consumption, maximal tolerated power, strength in both quadriceps and hamstrings, and quality of life. Both groups showed increased peak oxygen consumption and strength. “Our study has shown that high-intensity interval training combined with resistance exercise training induced an improvement in physical capacity and quality of life. Moreover, this study allowed patients, irrespective of their sex or EDSS [Expanded Disability Status Scale] score, to resume exercise autonomously,” the team wrote. "High-intensity interval training is well tolerated too and can be used in clinical rehabilitation with resistance training, in both men and women with and without disabilities."

First-line treatment with Copaxone (glatiramer acetate) benefits relapsing-remitting multiple sclerosis (RRMS) patients by boosting the number of anti-inflammatory immune cells and restoring the balance of regulatory immune cells, an Italian study shows. The study, “Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10…

Women who breastfeed for 15 months or longer may have a lower risk of developing multiple sclerosis (MS) than those who breastfeed for shorter periods or not at all, according to a recent study. The study also suggests that women who had their first…

People with multiple sclerosis have high levels of pro-inflammatory TH17 immune cells in their intestines that correlate with change in the micro-organism mix in their gut and the levels of their disease activity, a study reports. Researchers said the findings suggest that diet, probiotics and therapies that regulate TH17 cells could help treat MS. Probiotics are supplements containing beneficial bacteria. The study, “High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis,” was published in the journal Science. Research has shown that TH17 cells, also known as T helper 17 cells, play a role in the development of MS. In fact, they were the first harmful immune T-cells to infiltrate the central nervous system, according to studies in animals Where TH17 cells become activated has been unclear, however. Studies in mice suggested it was mainly in the small intestine. Research has also indicated that their activation increases the potential for a person to develop an autoimmune brain disease like multiple sclerosis. An autoimmune disease occurs when the immune system, which defends the body against disease, decides that a person's healthy cells are foreign, and attacks those cells. Researchers decided to see if the findings in mouse models of MS applied to people with the disease. They discovered a link between higher levels of TH17 cells in MS patients' intestines and autoimmune brain problems. They also found a correlation between higher levels of TH17 cells and changes in patients' gut microbiome. The team then identified which bacteria were changing in the gut. Patients with increased levels of TH17 cells and higher disease activity had a higher ratio of Firmicutes to Bacteroidetes bacteria and more Streptococcus strains in their gut, particularly Streptococcus mitis and Streptococcus oralis. Previous studies have shown that these species promote TH17 cell differentiation in humans. Cell differentiation involves a cell transforming from one cell type to another — usually a more specialized type. This dramatically changes a cell's size, shape, metabolic — or fuel-burning — activity, and responsiveness to signals. Some studies have suggested a link between T-cell differentiation and brain autoimmune diseases. “On the basis of our findings, we speculate that, under certain conditions, or because of still unknown virulence factors, these Streptococcus strains can colonize the small intestine and favor TH17 cell differentiation in the human gut mucosa [linings],” researchers wrote. In addition to more Streptococcus bacteria, the team detected lower levels of Prevotella bacteria in MS patients with disease activity than in healthy controls or patients with no disease activity. This decrease may also promote TH17 cell differentiation because “Prevotella is capable of producing the anti-inflammatory metabolite propionate that limits intestinal TH17 cell expansion in mice," the researchers wrote. Overall, the team concluded that “our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine.” The findings suggest that regulating TH17 cell expansion, along with changes in diet aimed at regulating intestinal linings, could be ways to help treat MS.

Patient questionnaires can be sensitive to signs of disease progression and worsening in neurological disorders like multiple sclerosis just as they are in other diseases, helping doctors to better predict clinical outcomes in patients, a study reports. Particularly, the study found that MS patients with higher scores on a specific disease questionnaire were nearly six times more likely to die within 10 years than those with lower scores, and that mortality risk also jumped among people whose scores rose on a second taking of same questionnaire. But the researchers cautioned that their study was not a tool for predicting mortality but a way to help patients be more active participants in their care. “Our research shows that by answering a set series of questions, patients can have an important role in predicting long-term prognosis in diseases like MS, and that these types of questionnaire should be used by doctors to get a better idea of the patient’s health,” Joel Raffel, study’s first author, from the Imperial College London, United Kingdom, said in a university news release written by Ryan O'Hare. “We hope that using patient-reported outcomes like these more and more will mean a shift towards empowering patients," he added. "They will be able to provide their own data, so rather than the doctor telling the patient how they are doing, it’s the other way around.” Among tools often used in the clinic are patient-reported outcomes; that is, questionnaires for patients that focus on their disease and treatment. But while these questionnaires have many uses, from screening for symptoms or evaluating treatment response to improving communications, they are often under-utilized when people have MS or other neurological diseases, "in part because it is not clear if PROs [patient-reported outcomes] relate to ‘hard clinical outcomes’ like disability or mortality," the team noted. Researchers wanted to determine whether the Multiple Sclerosis Impact Scale–29 (MSIS-29) — a 29-question survey assessing quality of life and disease impact over the previous two weeks — might serve as a way of predicting a patient's risk of death. The questionnaire was completed by 2,126 people, registered with the MS Society Tissue Bank in the U.K., beginning in 2004. Of these, 872 patients repeated it one year later. By 2014, the researchers reported that 264 of the original group of MS patients (12.4%) had died, and an evaluation revealed that MSIS-29 scores were associated with 10-year mortality risk regardless of age, gender, and disability score at the time the questionnaire was completed. Indeed, patients with high scores on the MSIS-29 questionnaire, indicative of a poor quality of life, were 5.7 times more likely to die within 10 years than those whose scores were lower. The mortality risk rose further among people whose MSIS-29 score worsened between the first and second year of answering the questionnaire. “Ideally, these questionnaires should be administered routinely, once a year in the clinic or online,” Raffel said. “This could help doctors to understand what issues the patients are facing and could also help to answer big research questions around prognosis and which of the available treatments we have for MS are working.” The team believes that questionnaire responses, together with usual clinical assessment tools like imaging data through MRI scans, could help doctors and patients choose the best course of treatment.

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.

According to a new clinical trial, the allergy treatment cetirizine fails to alleviate a flu-like condition that interferon-beta treatment generates in people with relapsing-remitting multiple sclerosis. The results, which surprised researchers, apply to flu-like syndrome, or FLS. Cetirizine is an over-the-counter medicine sold under the brand names Zirtec, Zyrtec, Reactine, and Triz. FLS affects roughly 75 percent of patients who take interferon-beta, also known as IFN-beta. It can cause fever, chills, muscle pain, weakness, and headache. The symptoms commonly occur three to six hours after an IFN-beta injection and last up to 24 hours. Although FLS usually subsides in the first three months of IFN-beta therapy, it persists in some patients, causing them to miss doses or even discontinue the treatment. Cetirizine is an antihistamine for hay fever and allergies. The purpose of the clinical trial was to determine whether cetirizine could alleviate RRMS patients' FLS. In order to determine study results, patients did self-assessments of how much discomfort their FLS caused them. There were no significant changes in the two groups' average self-assessment scores at four and eights weeks of treatment, suggesting that cetirizine does not offer significant benefits to RRMS patients with FLS. “The addition of a [cetirizine] to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to improve symptoms significantly compared with placebo," the team wrote. "FLS continues to be inadequately treated in many RRMS patients. Further investigations are needed to elucidate the underlying mechanisms of IFNβ-induced FLS and develop adequate strategies for prevention and treatment."

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.”

A recent study has found that continued use of Ampyra (dalfampridine extended-release, sold in the U.S. by Acorda Therapeutics) by patients with multiple sclerosis (MS) lowers both inpatient hospital visits and overall healthcare costs. Results from the study, titled “Inpatient Admissions and Costs Associated with Persistent…

The European Medicines Agency has restricted the use of Zinbryta (daclizumab) for relapsing multiple sclerosis after reports of patients experiencing severe liver damage and one dying of liver disease. The temporary order restricts Zinbryta to European Union patients with a highly active disease who have failed to respond to…

Advertising for stem cell therapies not supported by clinical research — often made directly to patients and sometimes promoted as a "cure" for diseases like multiple sclerosis or Parkinson's — is a growing problem that needs to be addressed and regulated, a team of leading experts say, calling such "stem cell tourism" potentially unsafe. Stem cell tourism is the unflattering name given to the practice of encouraging patients to travel outside their home country to undergo such treatment, typicaly at a private clinic. The article, titled "Marketing of unproven stem cell–based interventions: A call to action" and recently published in the journal Science Translational Medicine, was co-authored by scientists with universities and hospitals in the U.S., Canada, U.K., Belgium, Italy, Japan, and Australia. It focuses on the global problem of the commercial promotion of stem cell therapies and ongoing resistance to regulatory efforts. Its authors suggest that a coordinated approach, at national and international levels, be focused on "engagement, harmonization, and enforcement in order to reduce risks associated with direct-to-consumer marketing of unproven stem cell treatments." Treatments involving stem cell transplants are now being offered by hundreds of medical institutions worldwide, claiming efficacy in repairing tissue damaged by degenerative disorders like MS, even though those claim often lack or are supported by little evidence . They also noted that the continued availability of these treatments undermines the development of rigorously tested therapies, and potentially can endanger a patient's life. The researchers emphasize that tighter regulations on stem cell therapy advertising are needed, especially regarding potential clinical benefits. They support the establishment of international regulatory standards for the manufacture and testing of human cell and tissue-based therapies. "Many patients feel that potential cures are being held back by red tape and lengthy approval processes. Although this can be frustrating, these procedures are there to protect patients from undergoing needless treatments that could put their lives at risk," Sarah Chan, a University of Edinburgh Chancellor’s Fellow and report co-author, said in a news release. Chan and her colleagues are also calling for the World Health Organization to offer guidance on responsible clinical use of cells and tissues, as it does for medicines and medical devices. "Stem cell therapies hold a lot of promise," Chan said, "but we need rigorous clinical trials and regulatory processes to determine whether a proposed treatment is safe, effective and better than existing treatments." According to the release, the report and its recommendations followed the death of two children at a German clinic in 2010. The clinic has since been shut down. Certain stem cell therapies — mostly involving blood and skin stem cells – have undergone rigorous testing in clinical trials, the researchers noted. A number of these resulted in aproved treatments for certain blood cancers, and to grow skin grafts for patients with severe burns. Information about the current status of stem cell research and potential uses of stem cell therapies is available on the website EuroStemCell.

B-cells of patients with relapsing-remitting multiple sclerosis (RRMS) secrete substances that are toxic to both neurons and neuron-protecting myelin-forming cells, causing both kinds to die, according to a study. Despite analyses of numerous inflammatory and other factors believed to drive MS processes, researchers were unable to identify the molecules that are toxic, however. Dr. Robert Lisak of Wayne State University in Detroit, Dr. Amit Bar-Or of McGill University in Montreal and their teams are now working on identifying the factor, and learning if the process is also involved in progressive MS. Their study, “B-cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro,” was published in the Journal of Neuroimmunology. It demonstrated that B-cells gathered from the blood of RRMS patients killed lab-grown neurons and oligodendrocyte cells, which form myelin, a protecting coating for nerve cells. Deterioration of the myelin coating and the death of neurons are hallmarks of MS. An earlier study the team conducted indicated that B-cells from MS patients could kill oligodendrocytes. But since the experiments involved only three patients and three controls, the team scaled up their experiments to include 13 patients and an equal number of controls. Both rat and human neurons died when mixed with MS-derived B-cells. In contrast, B-cells from healthy people had little or no impact on the survival of the brain cells. Researchers also discovered that the secreted toxic molecules had no impact on other types of central nervous system cells — astrocytes and microglia. The toxins killed only neurons and myelin-producing cells. The B-cells triggered a process called apoptosis, or programmed cell death, researchers said. This is basically a suicide program. It tells a cell to die when exposed to stressful factors or toxins. The process differs from cell disintegration. Despite thoroughly screening about 40 inflammation-related substances, researchers were unable to identify any factors that caused the cells to die. The National MS Society and the Research Foundation of the MS Society of Canada funded the research, which the U.S. society highlighted in a news release. In the newest phase of the study, researchers will try to learn more about the processes underlying neuron and myelin-related cell deaths and identify the factors responsible. In addition to testing B-cells from progressive MS patients, the team will examine patients with other autoimmune conditions to see if the process is unique to MS or not. Researchers increasingly realize that B-cells are important to MS processes. This observation was underscored by U.S. regulators' approval of the B-cell depleting therapy Ocrevus (ocrelizumab) at treatment for both relapsing and primary progressive MS.

Genentech shared new insights into the workings of Ocrevus (ocrelizumab) and its effectiveness in reducing disease activity and slowing progression in relapsing and primary progressive multiple sclerosis (MS) at the recent 3rd Congress of the European Academy of Neurology (EAN). The new findings, previously reported here, built on analyses of information gathered during the three Phase 3 clinical trials assessing Ocrevus' safety and efficacy, as well as through monitoring patients in extension studies. The studies showed that nearly 40 percent of Ocrevus-treated relapsing patients and nearly 30 percent of primary progressive patients achieved NEPAD during the Phase 3 trials. In contrast, only 21.5 percent of those treated with Rebif and 9.4 percent receiving placebo achieved NEPAD — figures that demonstrate Ocrevus’ impact on patients’ lives, as well as Ocrevus’ ability to slow the decline in walking ability and other types of disabilities are comparable between patients with relapsing and primary progressive disease — data that demonstrate that the treatment acts on disease mechanisms that drive disability in both disease forms. How these effects play out in the long-term is the subject of ongoing research, as Genentech continues to follow these patients in an extension study. In addition, Ocrevus' prescription label strongly advises against pregnancy while on the treatment. Despite precautions, some women became pregnant during the trials. One of the meeting presentations narrated outcomes of these pregnancies; one healthy baby born at term and two ongoing pregnancies in women exposed to the drug. But while Genentech monitors women who become pregnant while on Ocrevus, the number of reported pregnancies is too small to draw conclusions about the treatment’s safety in pregnancy, and researchers do not know if Ocrevus also depletes B-cells in the fetus or in the baby born to a treated woman.

New analyses of how Merck’s Mavenclad (cladribine tablets) act to treat relapsing multiple sclerosis (MS) give researchers an entirely new picture of immune processes leading to the disease. Data showed that the drug lowers both immune B-cells and, to a lesser degree, T-cells. But the numbers of both cell…

A gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases like multiple sclerosis, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) report. It's a discovery that, they said, appears to be "a big step in the right direction." According to the study, published in the journal Science Immunology, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. “We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” Ciriaco Piccirillo, the study's lead author and an immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release. Tregs are known to be the immune system players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions. The FOXP3 gene is also well-known, and documented, to be essential for proper Treg cell function. However, the mechanisms by which FOXP3 gene is involved in Treg cell activities are still poorly understood. In the study, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions,” the research team — in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan — evaluated the impact of a FOXP3 gene mutation in autoimmunity response. Taking advantage of cutting-edge technology, the team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. “What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” said Piccirillo. “Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” added Khalid Bin Dhuban, the study's first author and a postdoctoral fellow in Piccirillo’s laboratory. The team developed a compound capable of restoring Treg cells' ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, two chronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including multiple sclerosis, type 1 diabetes, and lupus. "Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," said Piccirillo. “Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.” “This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Piccirillo added. “With this discovery, we are taking a big step in the right direction.”

MS patients who start treatment at a younger age, and whose condition requires hospitalization, are more likely to stop treatment, a Canadian study reports. The research, published in the journal Dovepress, dealt with the main reasons Canadian patients quit first-line injected disease-modifying therapies, or DMTs. It was titled “Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort.” DMTs can reduce MS activity, but patients must stick with them in order for them to be effective. “There is currently a paucity of clinical trial data on what happens to individuals when they discontinue DMT," the researchers wrote. "However, recent preliminary evidence from observational studies suggest increased relapses and disability in those who discontinue DMT." Researchers sought to identify MS patients at higher risk of discontinuing treatment. They looked at Manitoba Province's medical database to identify the types of drugs MS patients were taking, and for how long. The analysis covered 721 patients who received injected beta-interferons or Copaxone between 1996 and 2011, and whom doctors followed for at least a year. Teva manufactures Copaxone, whose generic name is glatiramer acetate. The mean age of the patients in the study was 37.6 years, and 74.2 percent were women. Researchers defined a discontinuation of a DMT as a 90-day or longer gap in treatment. A third of the patients were treated with beta-interferon-1b, either Bayer HealthCare's Betaferon/Betaseron or Novartis' Extavia. It was the first such therapy available in Manitoba. Twenty-three percent of patients received beta-interferon-1a, either Biogen's Avonex or Merck's Rebif. And 21 percent received Copaxone. The median time before a patient discontinued a DMT was 4.2 years. Although 62.6 percent of patients discontinued treatment at some point, 57.4 percent either reinitiated it or switched to a different DMT. Patients who were on DMT at least a year were more likely to stay with it than those who stopped in the first year. Importantly, patients who started a DMT at a younger age were more likely to stop taking it than older patients. “Our results are also consistent with previous work examining persistence for other chronic medication classes, including statins, antihypertensives, bisphosphonates, and oral antidiabetic agents, where the risk for discontinuing drugs declined in a linear fashion with age,” the researchers wrote. The team also found that 16 percent of patients had to be hospitalized overnight, with 3 percent of the cases due to MS-related complications. And these hospitalized patients were more likely to stop their DMT treatment earlier, the researchers said. Summing up, the team said: "Subjects who were younger when starting a DMT, had prior MS-related hospitalizations, were more recently diagnosed with MS, or had a greater lag time between their MS diagnosis and DMT initiation were more likely to discontinue therapy." Although "not all of the factors identified with discontinuing DMT" can be modified, "they may help practitioners enhance MS care by identifying individuals who may be at particular risk for DMT discontinuation," the researchers concluded.

The over-the-counter antioxidant lipoic acid slowed brain deterioration in patients with secondary progressive multiple sclerosis (SPMS), according to a pilot study. An Oregon Health & Science University research team conducted the study, “Lipoic acid in secondary progressive MS.” It was published in the journal Neuroimmunology and Neuroinflammation. A hallmark…

MSBase and icometrix have joined efforts in a large-scale project to identify imaging markers of multiple sclerosis (MS) that could help diagnose the disease in its early stages. The combination of magnetic resonance imaging (MRI) information collected from MS patients with clinical information from the MSBase Registry can offer new insights in disease progression, potentially leading to new predictive tools for MS. It may also promote more standardized use of imaging measures in clinical practice. With more than 52,000 MS patients, the MSBase Registry is an international database committed to collecting patients’ information as well as sharing, tracking and evaluating overall outcome data in MS and other neurological conditions. Until now, the MSBase Registry included only descriptive information regarding patients' imaging analysis results, with no access to full imaging data. This joint, large-scale project will include MRI scan data routinely acquired in clinical setting taking advantage of icometrix’s software platform, MSmetrix. “We wish to unlock the power of MRI for personalized monitoring in MS," Helmut Butzkueven, director of MSBase, said in a press release. "The MSBase Scientific Leadership group has selected MRI integration as the top strategic priority for MSBase. We believe that already conducted MRI scans represent an enormous missed opportunity, because advanced measurements to assess change over time from these scans are not currently in practical use.” Butzkueven said MSBase "will test the predictive power of this unlocking of MRI data in the first phase," with a total of 10,000 MRI data points in at least 3,000 MS patients from all over the world. The project is expected to identify disease progression markers that could help detect early signs of MS by MRI evaluation. This investigator-initiated collaboration between icometrix and the MSBase Foundation is being supported by three global pharmaceutical giants: Novartis, Biogen and Roche. “MRI measures play an essential part in the complex puzzle of MS,” said Danny Bar Zohar, global head of neuroscience development at Novartis. “Partnering with MS Base and icometrix in this exciting project will bring the acquisition of high-quality real world data to the next level, ultimately improving the outcome of people living with MS.”

Innate Immunotherapeutics' MIS416 has failed to help secondary progressive multiple sclerosis (SPMS) patients in a Phase 2 clinical trial. The company said it will continue testing the therapy, made up of natural compounds, to see if it can benefit any MS subgroups. Trial participants who received MIS416 had no meaningful improvements in neuromuscular function or the outcome of their disease, compared with those who took received a placebo. “It is disappointing that these results don’t show benefit for people with secondary progressive MS, for whom there are few treatment options,” Dr. Bruce Bebo, executive vice president of research at the National MS Society, said in a news release. Scientists hoped the injected therapy would modulate the activity of immune cells that affect the protective myelin coating around nerve cells, decreasing the inflammation and brain tissue damage associated with MS. Deterioration of the coating is a hallmark of the disease. The one-year trial (NCT02228213) tested the safety and effectiveness of MIS416 on 93 patients with SPMS in Australia and New Zealand. The patients randomly received MIS416 or a placebo once a week. There were no differences in the groups' scores on a disability index — the expanded disability status scale — or in brain volume changes detected by magnetic resonance imaging. In addition, there were no differences between in disease outcomes that patients reported. The self-reported barometers included the Multiple Sclerosis Impact Scale, the Neurological Fatigue Index, and the Brief Pain Inventory. "I am extremely disappointed by this outcome," Professor Pam McCombe, a principal trial investigator, said in a company press release. "Looking for measurable changes in patients with progressive MS using the assessment tools currently at our disposal is frustrating and complicated. We were hopeful that MIS416 would be an option to treat this group of patients who currently do not have effective treatment options." In addition to MIS416 failing to be effective, the group who received it had more treatment-related adverse events than the placebo group. The events were mainly related to the first dose, Innate said. The main problems were fever, chills, and muscle weakness. The company has been providing MIS416 to Australian MS patients under a compassionate use program. It said it will continue evaluating the safety and tolerability of the drug to see if it helps any subgroups of patients. Those findings will determine the future of the compassionate use program, it said. “These results are a shock, and definitely not what we were expecting based on our previous clinical experience with MIS416 and the reporting of treatment benefits we have received from many compassionate use patients over an extensive eight-year period," said Simon Wilkinson, Innate Immunotherapeutics' chief executive officer. "These data will be as distressing to them as they will be for all the stakeholders who were relying on the outcome of this study."

The multiple sclerosis therapy Tysabri could trigger melanoma, the Southern Network on Adverse Reactions (SONAR) has warned. Although its investigation failed to demonstrate that melanoma is more common among Tysabri-treated MS patients than in the general population, unusual features among the patients raise concerns about a possible link, the organization said. Contending that current monitoring efforts are inadequate, it suggested improvements that could generate a better understanding of the relationship between Tysabri treatment and cancer. The organization's report, published in the journal Cancer Medicine, was titled “Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions, also known as SONAR." SONAR is an organization that was formed in the Southern United States in 2010 to investigate adverse drug reactions that regulators might not be aware of. Its goal is to reduce the time it takes between detecting an adverse reaction and have regulators act on it. A case that a SONAR investigator came across led to the group investigating possible links between Tysabri and melanoma. A 43-year-old woman developed melanoma in her urethra, the tubing that drains urine from the bladder, after being treated with Tysabri for about two years. Melanoma is most often a skin cancer that is related to sun exposure, but the woman had no skin lesions. After extensive surgery, she relapsed and died when the cancer spread to other parts of her body. She had declined anti-cancer treatment. The case prompt SONAR to look for similar cases. Its investigators found seven studies that involved Tysabri-treated MS patients developing melanoma. In addition, they looked through the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) and the Tysabri Safety Surveillance Program. The surveillance program is part of the Tysabri Outcomes Unified Commitment to Health (TOUCH) database run by Tysabri's developer, Biogen, The research team found 137 cases in the FAERS database through April 1, 2014. The patients' average age was 45. Seventeen percent of the group developed tumors in locations not exposed to the sun, and nine died. The researchers said the database contained only about half the information it should have, such as tumor site, patients' family history of cancer, and earlier immunosuppressive treatment. Fifteen percent of the cases in the FAERS database were based entirely on information from the TOUCH database. Seventy-three percent were cases initially reported to FAERS but with TOUCH information added. Thirteen percent of the FAERS cases contained no additional information. Importantly, there was even less patient information in the TOUCH database than in the FAERS database. Out of eight items researchers believe a database should contain, TOUCH had information on two, on average. “The existence of the TOUCH Safety Surveillance Program, an FDA-mandated program, did not improve melanoma reporting,” the team wrote. This shortage of data stymies research into possible links between Tysabri treatment and melanoma, the researchers said. As an example, although the death rates in the databases were low, there was no information about survival in many cases, which could lead to flawed survival estimates. The investigation noted that patients received a wide range of Tysabri doses before they were diagnosed with melanoma. While some received only one or a few injections, others had been treated for a long time. These observations do not seem to support a link between Tysabri and melanoma, the team said. “A longer therapy duration would be expected if natalizumab caused melanoma via an immunologic pathway, unless existing nevi [lesions of the skin or mucus tissue] were already premalignant lesions,” the researchers wrote. But other information the team found seemed to suggest a Tysabri-melanoma link. For example, the average age of melanoma patients was much lower than that reported in the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. The average age in the institute's database is 63, compared with 45 in the FAERS database and 41 in cases in academic journals. In addition, many patients developed tumors in unusual places not exposed to sunlight. Finally, the low melanoma death rate in Tysabri-treated patients differed from that seen in the general population. All these factors suggest that melanoma after Tysabri treatment could differ from other types of melanoma, the researchers argued. While the molecular workings of Tysabri might promote melanoma growth, studies so far have not found a relationship between the drug and this cancer. In fact, some studies suggest that MS patients, in general, have a lower risk of melanoma than others. The team said more information on patients could give researchers a better understanding of the potential relationship between Tysabri and melanoma. The implication was that the standard of reporting in the FAERS and TOUCH databases could improve. To minimize the risk of patients who receive Tysabri developing melanoma, the researchers offered a number of suggestions for IV centers, physicians, patients, and educational programs. For instance, they suggested that all patients should have a skin examination before the start of treatment, and regular physical and skin exams while receiving Tysabri. While noting that risk of infection and the development of tumors can occur with all immunosuppressive treatments, the team said more studies are needed to explore the risk of Tysabri-treated patients developing melanoma.