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February 28, 2019 News by Jonathan Grinstein

#ACTRIMS2019 – No Evidence of Disease Activity Seen in POMS Adolescents Taking Rituximab, Small Study Shows

Data supporting the off-label use of rituximab in adolescents with pediatric-onset multiple sclerosis (POMS) was presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019. The session, titled “No Evidence of Disease Activity in the Majority of Pediatric-Onset Multiple Sclerosis Patients Receiving Rituximab,”…

February 28, 2019 News by Santiago Gisler

Axim Improves Delivery of Cannabinoids in Chewing Gums

Axim Biotechnologies announced that it has succeeded in microencapsulating cannabinoids (chemical compounds in cannabis) into the company’s patented chewing gums, which are used to treat several disease symptoms, including pain and spasticity associated with multiple sclerosis (MS). Since the active cannabinoids are degradable in the body, the company needed…

February 26, 2019 News by Iqra Mumal, MSc

Switching from Tysabri to Aubagio Can Help Lower Relapse Risk in MS Patients, Phase 4 Trial Shows

Stable patients with multiple sclerosis (MS) who transition from Tysabri (natalizumab) treatment to Aubagio (teriflunomide) have a lower relapse risk, a new study shows. The study, “Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy,”…

February 22, 2019 News by Iqra Mumal, MSc

New Compounds Offer Significant Anti-inflammatory, Neuroprotective Benefits in MS Mouse Study

Two newly identified variants of the known pharmaceutical agent chloroindazole showed significant anti-inflammatory and neuroprotective benefits in a mouse model of multiple sclerosis, a new study shows. Multiple sclerosis is an autoimmune, demyelinating disease of the central nervous system with no known cause or cure. Patients with MS characteristically show loss of the myelin sheath, a protective coat in nerve cells that helps increase cell-to-cell signaling. Several studies have suggested that estrogens — a type of hormone — are beneficial to the functioning of the central nervous system, and help regulate the immune system. Thus, they are attractive candidates for the treatment of MS. However, despite their potential to treat MS, estrogen-based therapies can have several undesirable side effects, such as feminizing male recipients and increasing the risk of developing breast and endometrial cancers in females. Interestingly, estrogens work by binding and activating two different types of receptors: the estrogen receptor (ER)α and ERβ. The cancer-inducing effects of estrogens are mediated mainly through estrogen receptor ERα. Hence, therapies that specifically target ERβ can bypass these deleterious effects. Chloroindazole (IndCl), a pharmaceutical agent, has up to 100-fold relative binding affinity for ERβ over ERα. IndCl has been shown previously to have beneficial effects on modulating the immune system and the central nervous system, and inducing myelination of nerve cells in mouse models of MS. Furthermore, IndCl and other ERβ-activating agents directly support the growth, differentiation (maturation), and overall myelination activity of oligodendrocytes, which are the nerve cells that produce the myelin sheath. Therefore, in order to optimize the benefits of IndCl, researchers developed and screened seven novel IndCl analogues for their ability to promote oligodendrocyte survival, growth, and differentiation. These analogues have a molecular structure closely similar to that of IndCl, but interact with estrogen receptors in subtly different ways. Among these seven compounds, researchers found two analogues — IndCl-o-chloro and IndCl-o-methyl — that stimulated growth and differentiation similar to the original IndCl. Next, researchers evaluated the benefits of these compounds in a mouse model of MS — the experimental autoimmune encephalomyelitis (EAE) mouse model — to determine whether they could alter the disease course, white matter pathology (level of demyelination), and inflammation. Results indicated that both compounds “ameliorated disease severity, increased mature OLs [oligodendrocytes], and improved overall myelination in the corpus callosum and white matter tracts of the spinal cord,” researchers wrote. Corpus callosum is a thick band of nerves that connect the left and right side of the brain. White matter tracts connect the cortex (the largest part of the brain) with other areas in the central nervous system. These beneficial effects were accompanied by a reduced production of the toxic, inflammatory molecules interferon-γ and CXCL10. Additionally, IndCl-o-methyl also reduced the levels of peripheral interleukin (IL)-17, a molecule that strongly induces inflammation. Furthermore, IndCl and both analogues upregulated the expression of a compound called CXCL1, which is associated with increased production of oligodendrocytes. Not only were these two newly identified compounds equivalent to IndCl, but the two analogues performed better in reducing disability and encouraging remyelination than the original compound, and without any obvious side effects. “The o-Methyl and o-Chloro IndCl analogues represent a class of ERβ ligands that offer significant remyelination and neuroprotection, as well as modulation of the immune system; hence, they appear appropriate to consider further for therapeutic development in multiple sclerosis and other demyelinating diseases,” the researchers concluded. “We believe we created a drug that does two things really well, modulating inflammation and allowing axon remyelination. No other drug on the market can do these two things simultaneously,” Seema K. Tiwari-Woodruff, said in a press release written by Stacy Kish. Tiwari-Woodruff is the study's lead author. “The most amazing part of the study is that these new analogues of a known estrogen modulator, chloroindazole, are superior in treating mouse model of multiple sclerosis,” she added. The team has patented the analogues, and hopes to begin further pharmacological and toxicity studies soon.

February 21, 2019 News by Vijaya Iyer, PhD

FDA Warns Against Plasma Transfusions from Young Donors Being Used to Treat MS and Other Diseases

The U.S. Food and Drug Administration (FDA) has warned against the use of plasma transfusions from young donors to alleviate or treat the symptoms of multiple sclerosis or other diseases, noting such transfusions have no proven clinical benefit and carry known health risks associated with their use. Plasma is the liquid component of blood, containing proteins that help in clotting, and can be used to treat bleeding disorders and cases of trauma. But its use in transfusions as a means of treating conditions ranging from multiple sclerosis, dementia, Alzheimer’s, Parkinson’s, heart disease and post-traumatic stress disorder are of concern, the FDA said in issuing its statement of Feb 19. "We have significant public health concerns about the promotion and use of plasma for these purposes," the FDA statement reads. "[W]e’re alerting consumers and health care providers that treatments using plasma from young donors have not gone through the rigorous testing … [necessary] to confirm the therapeutic benefit of a product and to ensure its safety." Scott Gottlieb, the FDA's commissioner, and Peter Marks, director of its Center for Biologics Evaluation and Research, jointly issued the statement cautioning healthcare providers and the public that plasma infusions — being done at "a growing number of clinics" in several U.S. states — are not an FDA-approved or recognized treatment for aging, memory loss, multiple sclerosis, or other diseases. FDA-approved treatments largely come through clinical trials overseen by researchers and independent boards, and performed under an investigational new drug (IND) application that helps to ensure patient safety. “Our concerns regarding treatments using plasma from young donors are heightened by the fact that there is no compelling clinical evidence on its efficacy, nor is there information on appropriate dosing for treatment of the conditions for which these products are being advertised,” the statement notes. According to the FDA, large volumes of plasma might be also be needed for such transfusions and that volume can pose significant risks, including allergic reactions, infections, and heart and respiratory problems. The agency also expressed concern that such transfusions could discourage patients from taking medications or other treatments known to be safe and effective for their condition. According to the agency, some "establishments" across the country are recommending young donor plasma infusions and "touting" them "as cures and remedies," while sometimes "charging thousands of dollars." The FDA advises patients to consult with their treating physician before opting for any treatment to confirm that it is approved for use, meaning its safety and effectiveness have been demonstrated. “Simply put, we’re concerned that some patients are being preyed upon by unscrupulous actors touting treatments of plasma from young donors,” the FDA statement reads. It also asks that patients who have undergone a plasma transfusion report any ill effects to its MedWatch program, which tracks adverse events related to treatments.

February 20, 2019 News by Patricia Inacio, PhD

Early Use of High-efficacy DMTs of Long-term Benefit to MS Patients, Real-world Study Reports

Multiple sclerosis (MS) patients given intensive disease-modifying therapies early in their disease course have more favorable long-term outcomes than those treated with an escalating regimen, real-world data shows. The study, “Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis,” was published in the journal …

February 20, 2019 News by Jonathan Grinstein

Vitamin B12, Folic Acid Supplements Yield Multiple Benefits for MS Patients

Vitamins B12 and B9 (folic acid) supplements can lower levels of homocysteine (a common amino acid), improve anemia status, and boost self-reported physical health in patients with multiple sclerosis, according to new research. The study suggests a potential role for these two vitamins in improving the quality of life of MS patients. Despite treatment, MS patients often experience symptoms that interfere with their daily lives. Many patients have turned to dietary supplements with the hope they would reduce the severity of their symptoms. There is substantial literature suggesting the benefits of various supplements for MS, including vitamin B12 and folic acid. Homocysteine, of which high levels are associated with heart disease and detrimental effects in the nervous system, can be more prevalent in MS patients compared to healthy individuals. That suggests homocysteine is "one of the causative factors in the pathogenesis [development] of MS," researchers wrote. Lack of vitamin B12 — naturally found in meat, fish, poultry, eggs, and dairy products — can lead to a disruption in myelination, the process of forming a protective myelin coat around nerve cells. The loss of myelin is a hallmark of MS. A lack of folic acid, together with too little vitamin B12, has been linked to neurological symptom onset in MS patients. Meanwhile, vitamin B12 and folic acid supplements have shown promising results among these patients. In addition, MS patients are known to have an increased risk for the development of megaloblastic anemia — a condition in which the bone marrow produces unusually large, immature red blood cells referred to as megaloblasts. The most common causes of megaloblastic anemia are a deficiency of either vitamin B12 or folic acid. Based on these observations, researchers from Urmia University of Medical Sciences and Kermanshah University of Medical Sciences, in Iran, studied the effects of vitamin B12 and folic acid supplements in  relapsing-remitting multiple sclerosis (RRMS) patients. The team looked specifically at serum homocysteine levels, anemia status, and quality of life. This double-blinded clinical trial (IRCT2015100313678N7) enrolled 50 RRMS patients (age 20-40 years), who were divided into two groups: the vitamin group, which received three doses of 1 mg vitamin B12 injection (spaced a month apart) plus 5 mg folic acid tablets daily; and the placebo group, which received neutral saline injections. All participants completed two quality-of-life questionnaires, one geared toward physical health and the other toward mental health, at the start and end of the study. Blood samples were collected from all participants, and blood pressure readings were taken. Results showed a drop in average homocysteine blood serum levels in the vitamin group, which may be indicative of an improvement in nervous system health. Researchers also observed a decrease in mean corpuscular volume (MCV) in the vitamin group, which is indicative of improved anemia status. At the end of the study the vitamin group showed improvements in both physical and mental fields in the quality-of-life questionnaires. However, RRMS patients in the control group (without vitamin supplements) also had an increase in the quality-of-life questionnaire for mental health, obscuring any conclusions on the effect of vitamin supplements in MS patients’ mental health. “Results of the present study have shown that homocysteine levels, anemia status, and eventually the quality of life of patients with MS can be significantly improved by administration of 1 mg of vitamin B12 monthly and adding rich-food sources of folic acid on their diet,” the researchers wrote. The team nonetheless emphasizes that "further studies in the field of MS dietary patterns must be conducted."

February 18, 2019 News by Jonathan Grinstein

Protein That Turns Certain T-cells into Inflammatory Agents Identified in Early Study

A protein called Satb1 appears to be the "on switch" that turns a type of T-cell called Th17 from its typical protective role into one that is disease-causing, and key in the development of multiple sclerosis (MS) and other inflammatory autoimmune disorders, a study reports. These findings suggest that Satb1 may be a therapeutic target for autoimmune diseases like MS. The research article, “Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation,” was published in the journal Nature Communications. Immune cells called T-helper 17 (Th17) cells play a range of roles in immunity, including protecting against infecting pathogens — bacteria, viruses, and other microorganisms that can cause disease. But Th17 cells are also players in the development of such autoimmune diseases as MS, psoriasis, inflammatory bowel disease, and rheumatoid arthritis. This is because Th17 cells can be stimulated to become T-cells that engage in pathogenic, or disease-causing, immune programs. How Th17 cells switch from their typical and helpful immunity role to that of a pathogenic actor has not been resolved, although it is thought critical to treating inflammatory autoimmune diseases. An international team led by researchers at Osaka University and Kyoto University, in Japan, tried to identify the mechanism behind the disease-causing program of Th17 cells. To do so, they built upon previous findings showing that a protein regulator called Satb1 is important in the development of Th17 cell subsets. "We have known for some time that Satb1 is indispensable for the development of T-cells in the thymus. However, how it is involved in the regulation of pathogenic processes of Th17 cells in inflamed tissues had not been examined," Keiko Yasuda, MD, the study's lead author, said in a press release. Researchers used a standard mouse model of MS, called experimental autoimmune encephalomyelitis (EAE) mice. These animals had genetically-modified Th17 cells that lacked Satb1. Researchers tested how Th17 cells lacking Satb1 acted when subject to inflammatory conditions, and how they were stimulated to activate a "pathogenic effector program." Interestingly, these modified mice were resistant to the development of EAE, or MS-like, disease. Researchers saw fewer Th17 cells infiltrating the animals' spinal cord. Also, Th17 cells lacking Satb1 showed poorer production of key pathogenic signaling molecules in autoimmunity, notably one called granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is known to cause localized tissue inflammation in MS and other inflammatory autoimmune diseases. Researchers went on to show that Satb1 can act as a switch between benign and pathogenic Th17 cells, depending on their exposure to healthy or inflammatory conditions. They found molecules that boost the pathogenicity of Th17 cells, such as Bhlhe40, and molecules that promote normal immune function, such as PD-1.  Of note, PD-1 is shut down when Th17 cells engage in their pathogenic effector program. These results showed Satb1 to be a key regulator of Th17 cell pathogenicity in these MS mice. Halting Th17 cells from making Satb1 may offer a way of treatting various autoimmune diseases. “Together, our findings, in addition to providing novel insights into the molecular mechanisms underlying the pathogenic program of tissue Th17 cells in mice, may help design novel immunotherapeutic approaches such as small molecule modifiers of Satb1 for the treatment of autoimmune diseases,” the researchers wrote. Future studies are needed to confirm these results in people. A previous study in people also suggested a link between Satb1 and the pathogenic function of Th17 cells in the central nervous system of MS patients. Overall, "our results suggest that manipulating Satb1 gene expression in Th17 cells could form the basis of novel treatments for various autoimmune diseases caused by Th17 cells. If we can prevent the pathogenic processes of Th17 cells, we may be able to alleviate or even eliminate disease symptoms," concluded Shimon Sakaguchi, PhD, one of the study's senior authors.

February 15, 2019 News by Larry Luxner

Newly Published NMSS Study Confirms Nearly 1 Million Americans Have MS

It’s finally official: Around 900,000 Americans and quite possibly more than that have multiple sclerosis (MS) — easily double the long-accepted figure of 400,000. Since MS News Today first reported on this finding in November 2017, the National Multiple Sclerosis Society (NMSS) study, which reached that conclusion, has…

February 14, 2019 News by Santiago Gisler

Continuous Use of Gilenya for Up to 3 Years Can Lead to 50% Drop in Annual Relapse Rates, Real-world Study Says

Multiple sclerosis patients who began treatment with Gilenya and stayed with it continuously showed a more than 50 percent reduction in annual relapse rates, a real-world study following these people for up to three years found. Gilenya, marketed by Novartis, is an oral disease-modifying treatment for relapsing-remitting multiple sclerosis , approved in 2010. It acts by binding and modulating receptors — called sphingosine-1-phosphate receptor — on lymphocytes (adaptive immune cells). By binding to these receptors, Gilenya prevents lymphocytes from leaving the lymph nodes and reaching the brain and spinal cord, and so lower lymphocyte-induced inflammation and damage. Although several clinical trials have reported reduced annualized relapse rates (ARRs) upon treatment with Gilenya, few long-term real-life studies have examined the relapse rate reductions over a long term. A team, led by Novartis researchers and a scientist at Central Texas Neurology Consultants, collected MS patient data from the MarketScan database, a U.S. claims database including medical and pharmacy claims (bills submitted to health insurance providers), between 2009 and 2016. Among 9,312 MS patients in the database with at least one filled Gilenya prescription, 1,599 adults (mean age, 46) met the study's inclusion criteria, including having at least one inpatient or two outpatient claims, and a total of four years of continuous health plan enrollment. Among these 1,599 patients, all used Gilenya for one year (cohort 1), 1,158 (72.4%) took Gilenya continuously up to the start of year two (cohort 2), and 937 (58.6%) used the therapy up to the start of year three (cohort 3). Baseline analysis — measures taken at the study's start — showed that the most common MS-linked symptoms were disorders of the optic nerve and visual pathways (reported in 22-24%), followed by fatigue/malaise (20-21%). Hypertension (20-21%) and depression (15-16%) were the most common physical and mental comorbidities, respectively. The mean annualized relapse rates (AARs) at baseline in these three groups of patients — cohorts 1 to 3 — ranged between 0.48 and 0.51. A consistent reduction in ARRs was seen in all three groups: cohort 1 had a 0.25 ARR at the close of the first year, for a 51% reduction from the baseline rate; cohort 2 a 0.22 ARR at the start of year two, for a  54% lowering in relapse rates from baseline; and cohort 3 had 0.23 ARR at the third year, amounting to a 53% reduction. As expected, when researchers calculated ARRs among patients with continuous Gilenya use over these three years, they found a greater reduction in annual relapse rates. Mean ARRs in continuous-use patients were 0.19 (a 61% reduction) during the first year, 0.18 (a 62% reduction) during the second year, and 0.18 (a 61% reduction) at the start of the third year. “This retrospective claims database study found that patients with MS who received fingolimod [Gilenya] therapy experienced a durable and sustained reduction in relapse rates over a 3-year period,” the researchers wrote, with findings representing “a durable reduction in relapse rates by [more than] 50%.” Reasons that some patients discontinued treatment were not a focus of this study, they added.

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