Alice Melão, MSc,  —

Multiple sclerosis (MS) can have severe implications on the lives of European women with the disease, finds a new report, affecting their education, their careers and their relationships. This disproportionate burden of MS in women versus men was the focus of a study, “The Socioeconomic Impact of…

Celgene‘s investigative drug ozanimod has been shown to be more efficient than an intramuscular injection of interferon beta-1a (marketed as Avonex by Biogen) in reducing relapses and disease progression in patients with relapsing multiple sclerosis (MS), according to results of the two-year Phase 3 RADIANCE trial. The findings were…

Gilenya (fingolimod) was seen to significantly reduce relapses in children and teenagers with multiple sclerosis (MS), according to data from a Phase 3 study — the first successfully conducted in pediatric patients. Novartis, the therapy’s developer, is preparing to file requests for Gilenya to be approved to…

Older patients with secondary progressive multiple sclerosis (SPMS) have reduced risk of experiencing disease relapse, according to a study presented at the 7th Joint ECTRIMS-ACTRIMS Meeting, being held Oct. 25-28, in Paris, France. The study, “Relapses in patients with secondary progressive MS: a matter of disease duration…

Inhibiting a protein found at high levels in immune cells located in the brain can rejuvenate myelin, the protective coating around nerve cells, according to a multiple sclerosis study in mice. Blocking the protein, known as the colony-stimulating factor 1 receptor, or CSF1R, can also prevent the immune cells from…

Using strategies to promote intellectual enrichment among patients with pediatric-onset multiple sclerosis could be essential to achieving better cognitive, social, and professional performances during adult life, according to researchers at the University of Florence in Italy. The finding was the subject of an oral presentation titled, “Cognitive reserve is…

An immune signaling protein called interleukin-35 has anti-inflammatory properties that scientists might harness to develop a therapy for multiple sclerosis and other autoimmune disorders, according to two studies. Researchers at the National Eye Institute of the National Institutes of Health discovered that a subunit of interleukin 35, which is also known as IL-35, significantly reduced inflammation in mouse models of eye inflammation and multiple sclerosis. Immune B-cells produce IL-35 to communicate with, and regulate the behavior of, surrounding cells. In a previous study, the research team found that the protein could inhibit inflammation in the eyes of animals with autoimmune uveitis, or inflammation of the inner layers of the eye. An autoimmune disease is one in which the immune system attacks healthy cells instead of invaders. A drawback of trying to use a synthetic version of IL-35 as a therapy is that it's difficult to produce because of its complex structure and it's unstable in a solution. Natural IL-35 is composed of two subunits, IL-12p35 and Ebi3, which bind to create the full protein. The team wondered if they could use a subunit, instead of the full protein, as an anti-inflammatory agent. Their study, “IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease,” was published in the journal Nature Communications, They demonstrated that the IL-12p35 subunit could generate anti-inflammatory effects similar to those of the full IL-35 protein. Giving IL-12p35 to mice with uveitis promoted the expansion of immune B-cells that counteract autoimmune responses, reversing the animals' eye symptoms. In the second study, researchers discovered that the subunit tempered inflammation in a mouse model of multiple sclerosis. Giving the animals IL-12p35 every other day for up to 12 days promoted immune cell proliferation that inhibited inflammation in the mice's brains and spinal cords, improving their symptoms. The research demonstrated IL-35 and its subunit's potential to treat nerve-inflammation disorders. The team published its findings in the journal Frontiers of Immunology. The article is titled “IL-12p35 inhibits neuroinflammation and ameliorates autoimmune encephalomyelitis.” The team is now looking at IL-12p35's ability to treat other degenerative eye diseases, such as diabetic retinopathy and macular degeneration.

Inhibiting an enzyme prevented mice from developing a multiple sclerosis-like disease, a European study reports. The finding about HDAC1, a member of the histone deacetylases family of enzymes, could open up new therapy possibilities for MS. Researchers published their study, “A T cell-specific deletion of HDAC1 protects against experimental…

Nimbus Therapeutics and Celgene have agreed to work together to identify potential therapeutic compounds that can specifically target Tyk2 and STING — two proteins involved in inflammation and innate immune response. This strategic collaboration can open new therapeutic avenues for the treatment of multiple sclerosis (MS) and several autoimmune disorders. Nimbus, headquartered in Cambridge, Massachusetts, applies chemical computational analysis to identify and develop new compounds with potential for therapeutic use in a range of diseases. Two Nimbus immunology programs are already covered under the newly established agreement: one developing inhibitors of Tyk2 and antagonists of STING protein. Tyk2, or tyrosine kinase 2, mediates the signaling of several pro-inflammatory proteins, including interleukin (IL)-23, IL-12 and type-I interferons. Inhibiting this enzyme can stop signals from passing through. This can potentially impair inflammatory response. STING, or stimulator of interferon genes, is an important activator of immune responses. As such, finding ways to block its activity can help prevent autoimmunity and reestablish immune response balance. Under their accord, Nimbus will control the program's research and development; Celgene will have the option to acquire each program covered by the alliance.

Synthon’s prefilled syringe with 40 mg/ml of glatiramer acetate — the generic version of Teva Pharmaceutical’s Copaxone 40 mg — has received regulatory clearance in all 28 member states of the European Union (EU) plus Iceland, Liechtenstein and Norway to treat relapsing-remitting multiple sclerosis (RRMS). The low-dose…

Antisense Therapeutics announced that it is proceeding with a Phase 2b clinical trial of ATL1102, its lead candidate to treat multiple sclerosis, after the U.S. Food and Drug Administration (FDA) lifted a clinical hold it had placed on the company’s request — in the form of a trial application or IND —…

Fast Forward, a non-profit subsidiary of the National Multiple Sclerosis Society, will give financial support to TG Therapeutics to advance TGR-1202 (umbralisib) into preclinical testing as a potential oral therapy for progressive forms of multiple sclerosis. The support, whose value was not specified, is part of a Sponsored Research Agreement between Fast Forward and the company. Research work will be led by Lawrence Steinman, MD, a professor of pediatrics, neurology, and neurological sciences at Stanford University. TGR-1202 is an orally administrated inhibitor that blocks a signaling enzyme called PI3K delta. Immune cells such as B-cells have high levels of this enzyme, which is thought to be important for cell proliferation and survival. "We look forward to evaluating umbralisib [TGR-1202]'s effect on our preclinical progressive MS models in hopes to move umbralisib closer to clinical development in MS," Steinman said. The approval of Ocrevus (ocrelizumab), by Genentech, to treat primary progressive and relapsing multiple sclerosis underscored the potential of B-cell-targeted therapies for MS patients. As a result, investigative drugs that also aim to bolster B-cell survival or activity, such as those being developed by TG Therapeutics, are an attractive approach to potentially treating patients. Another potential treatment by the company — an engineered antibody, TG-1101 — targets a specific sequence on the CD20 protein found on immune B-cells. This infusion therapy is now in two Phase 3 clinical studies for relapsing multiple sclerosis, ULTIMATE I and ULTIMATE II. Both are currently enrolling patients at sites in Kentucky, Tennessee, and New York.

Active brain inflammation appears to be one of the causes driving anxiety and depression in patients with relapsing-remitting multiple sclerosis (RRMS), finds an Italian study published in the journal Neurology. RRMS is the most common form of the disease when patients are initially diagnosed. Multiple sclerosis patients…

Researchers at the University of Nottingham and neurologists at Nottingham University Hospitals NHS Trust in England will be working with a team from the Cleveland Clinic in Ohio to better understand the best therapeutic strategy for multiple sclerosis (MS) patients. The $10.6 million international clinical trial was one of five…

Two molecules known to regulate cellular signaling contribute to the underlying mechanism of progressive multiple sclerosis, found a recent study conducted by investigators at Oregon Health & Science University and Yale University School of Medicine. These two proteins are related to each other, as they participate in the same cellular signaling process that regulate the immune system's response. Previous studies have blamed them for the worsening of several autoimmune and inflammatory disorders including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. The research team found that patients with progressive MS had higher levels of MIF and D-DT proteins than those with the relapsing-remitting form of the disease. In addition, these proteins inflamed the central nervous system, making patients sicker. An analysis of the genes that encode the proteins revealed that higher levels of MIF were linked to the presence of two genetic variants that are more frequent in patients — particularly males — with progressive disease. Researchers confirmed their findings with animal models of MS-like disease that were genetically engineered to lack MIF and D-DT proteins. Taken together, this finding suggests that a simple genetic test could identify patients carrying the MIF genetic susceptibility — and therefore more likely to develop a severe form of MS. This study was partially funded by the National Institutes of Health, the National Multiple Sclerosis Society, the Rocky Mountain MS Center Tissue Bank and the U.S Department of Veterans Affairs.

The U.S. Patent and Trademark Office has issued a patent for human embryonic stem cells derived mesenchymal stem cells, called hES-T-MSC or T-MSC, and for their method of production. This newly patented technology was developed by ImStem Biotechnology in collaboration with the University of Connecticut (UConn) to advance new…

Women with low levels of vitamin D in their blood are more likely to develop multiple sclerosis (MS) later in life, finds a large-scale study on women in Finland. The study, “25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort,” appeared in the journal…

The Patient-Centered Outcomes Research Institute has awarded $38 million in grants for five projects that compare the effectiveness of different multiple sclerosis treatment strategies. A key aim of the research is to improve knowledge about the therapies to help doctors and patients choose the healthcare option that best meets patients’ needs. The…

GT Biopharma has acquired licensing and development rights for PainBrake —  Accu-Break Pharmaceuticals’ non-opioid pain medication to treat dysesthesia and pain caused by nerve damage in multiple sclerosis (MS). “I am looking forward to initiating the development of PainBrake as we anticipate that many patients with difficult-to-treat neuropathic pain could…

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.

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…

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…

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."

Therapeutic horseback riding, also known as hippotherapy, when combined with standard care regimens significantly reduces fatigue and spasticity in multiple sclerosis. It also improves balance and quality of life, according to a German study. Hippotherapy takes advantage of a horse's natural movements to develop a patient's muscle tone and improve breathing, while strengthening the torso muscles. Horseback riding also improves balance control, coordination and gait, while boosting a patient's social communication skills, which can benefit self-esteem. “Hippotherapy as a complementary treatment can be defined as one-patient-one-horse physiotherapy treatment with and on the horse,” researchers wrote. Team leaders Vanessa Vermöhlen and Petra Schiller of the University of Cologne evaluated the benefits of half-hour weekly sessions of hippotherapy in combination with standard care. They randomly assigned 70 MS patients with lower limb spasticity to either an intervention group that did 12 weeks of hippotherapy, or a control group that received only standard therapy. The team evaluated the impact therapeutic horseback riding had on balance, measured by the Berg Balance Scale (BBS). They also measured its effect on other multiple sclerosis symptoms and signs, including fatigue, quality of life, pain, and spasticity. Overall, the team found that those who received hippotherapy plus standard care improved their BBS scores by 4.8 points after six weeks of therapy, and 6.4 by the trial's end. These increases were significantly higher than those achieved by the control group (2.9 points at six weeks and 3.1 points at 12 weeks). Although this represents a difference of only 3.3 points after 12 weeks, it still reflects a relevant change in patients' balance control capabilities, the authors said. In addition, the researchers also recognized significant improvements in fatigue, spasticity and quality of life of those undergoing hippotherapy plus standard care compared to those on the control group. The observed beneficial effects of hippotherapy validate previous reports that showing that activities with horses could help adults and children improve their balance, gait and psychomotor abilities.

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."

An exoskeleton developed by Harvard University researchers could restore multiple sclerosis patients’ balance and some of their walking capability, according to a study. ReWalk Robotics is moving toward commercializing the system, developed at Harvard’s Wyss Institute for Biologically Inspired Engineering. In addition to MS patients, the exosuit should help people with Parkinson’s and other neurodegenerative conditions,…

Resistance training like weight lifting can protect or even regenerate the nerve cells of relapsing-remitting multiple sclerosis patients, slowing the progression of the disease, according to a clinical trial. A hallmark of MS is the brain shrinking faster than normal, and findings from this trial indicates that resistance training can slow the shrinking or even make some brain areas grow. Research has shown that physical training benefits MS patients, helping them alleviate many symptoms, including excessive fatigue and balance control problems. Recent studies suggest that exercise can have a disease-modifying role in MS. This means physical activity can be an important adjuvant, or add-on therapy, for standard-of-care regimens. Researchers followed 35 patients with relapsing-remitting MS for 24 weeks. Eighteen patients did resistance training twice a week, consisting of four lower- and two upper-body exercises. The other 17 patients struck with their normal routines. Before and after the 24 weeks, doctors took magnetic resonance imaging scans, or MRIs, to evaluate patients' brain structures. After the 24 weeks, the scans showed less brain shrinkage in those who had resistance training. Some of their cortical brain regions were also thicker — an indication they were growing. It is not clear why exercise benefits MS patients' brains, nor if exercise has the same effect on all patients. Additional studies are needed to clarify its therapeutic effect, the researchers said. That knowledge could help improve current MS therapies.

The neurotransmitter glutamate triggers most brain signals by activating proteins on the surface of neurons called glutamate receptors. Columbia University Medical Center researchers have taken the first 3D images of the AMPA-subtype glutamate receptors involved in several brain activities, including memory and learning. By increasing scientists' understanding of how the receptors work, the images could offer insight into the role that faulty receptors play in the development of neurodegenerative disorders such as multiple sclerosis, Alzheimer’s, and Parkinson’s. And that insight could lead to therapies. “With our new findings, we can now, for the first time, visualize how the neurotransmitter glutamate opens glutamate receptor ion channels,” Dr. Alexander Sobolevsky, an associate professor of biochemistry and molecular biophysics at Columbia, said in a news release. “This is the fundamental process that directly affects learning and memory, and finding its structural determinants has been the primary goal of molecular neuroscience since the ‘90s," added Sobolevsky, the senior author of the study. For the brain to work properly, neurons need to communicate with each other. To do that, they use neurotransmitters, small compounds that pass from one cell to a receptor on another cell. Glutamate is the neurotransmitter involved in many of these communications, and glutamate receptors are the structures that gather up many of the signals. Several types of glutamate receptors participate in cognitive functions. AMPA receptors – a subgroup of glutamate receptors – are known for their fast activity, opening and closing in less than a millisecond. Because they work so fast, they are involved in rapid brain responses, such as rapid perception and reaction to the surrounding environment. For years, researchers have tried to understand how AMPA receptors work. In previous studies, Sobolevsky's team learned how the receptors regulated both the speed and strength of cell communications. In the recent study, the researchers used advanced imaging techniques developed by Dr. Joachim Frank to record the actions of the AMPA receptors. Frank, a professor of biochemistry and molecular biophysics, and biological sciences, was a co-author of the study. The images showed that AMPA receptors open in the presence of glutamate or a similar signaling compound. The mechanism can be compared to a camera’s iris, or aperture. The signaling particles pass through the opening, triggering electrical signals necessary for brain activity. “These new fundamental discoveries have implications for our understanding of neurotransmission by glutamate, our brain’s major neurotransmitter,” said Edward C. Twomey, a Ph.D. candidate who was the first author of the study. “Understanding these processes will impact future studies on glutamate receptor signaling in neurodegenerative diseases as well as drug design.”

Canadian oilman Hank Swartout made a fortune as longtime founder and CEO of Precision Drilling. The Calgary native mortgaged his house to start the company, which by the time he left in 2009 had annual sales of $7 billion. But an early diagnosis of multiple sclerosis (MS) at the age…

Eli Lilly and Nektar Therapeutics have established a development and commercial agreement for the investigational T-cell stimulator therapy NKTR-358 for the treatment of autoimmune disorders, including multiple sclerosis. NKTR-358, discovered and initially developed by Nektar, has the potential to modulate immune system responses to re-establish an immune balance in patients with autoimmune disorders. The treatment targets the interleukin 2 receptor complex (IL-2R) that is expressed on the surface of a subset of immune cells called regulatory T-cells, or Tregs. NKTR-358 activity stimulates the proliferation of Tregs, which in turn will regulate the activity of other immune cells that are uncontrolled and are responsible for the underlying mechanisms of autoimmune disorders. "We look forward to working with Nektar to study this novel approach to treating a number of autoimmune conditions," Thomas F. Bumol, PhD, senior vice president of biotechnology and immunology research at Eli Lilly, said in a press release. "NKTR-358 is an exciting addition to our immunology portfolio and reinforces Lilly's commitment to sustain a flow of innovative medicines in our pipeline." Bumol added. Under the agreement, Lilly and Nektar will continue to jointly develop NKTR-358. Nektar will be responsible for completing the ongoing Phase 1 clinical study; and Phase 2 clinical development costs will be shared by the two companies, with Lilly covering 75 percent of the costs and Nektar the remaining 25 percent. Nektar will have the option to take part of the Phase 3 development of NKTR-358 on an indication-by-indication basis. "We are very pleased to enter into this collaboration with Lilly as they have strong expertise in immunology and a successful track record in bringing novel therapies to market," said Howard W. Robin, president and CEO of Nektar. "Importantly, this agreement enables the broad development of NKTR-358 in multiple autoimmune conditions in order to achieve its full potential as a first-in-class resolution therapeutic." Based on the announced agreement, Lilly will pay an initial amount of $150 million to Nektar, which will also be eligible to receive up to $250 million from additional development and regulatory milestones. In the future, Nektar may also receive royalties from the product depending on its investment in NKTR-358’s Phase 3 development and future product sales. Lilly will cover all costs of global marketing of NKTR-358, and Nektar will have an option to co-promote the drug in the United States.