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Enzyme Regulates Development of Specific T-cells That Contribute to Autoimmune Disease, Study Suggests

A new study highlights a crucial role for the enzyme protein tyrosine phosphatase N2 in the development of early immune T-cells, and suggests that decreased levels of this enzyme can lead to the production of subsets of T-cells that contribute to the development of autoimmune diseases such as multiple sclerosis. T-cells, which are a type of immune cells that fight infection, are composed of multiple subsets that have different roles in immunity. Researchers at Monash University set out to characterize the role of PTPN2 in early T-cell development and in the development of T-cell subsets αβ TCR and γδ TCR. To do this, researchers deleted the gene coding for PTPN2 and looked at the resulting T-cell population. Results demonstrated that the deletion of PTPN2 led to the production of γδ T-cells with pro-inflammatory properties that have been associated with many autoimmune diseases by inhibiting certain pathways that regulate proper T-cell development. “This is an important advance in our understanding of critical checkpoints in T-cell development,” Tony Tiganis, principal research fellow in the Department of Biochemistry and Molecular Biology at Monash University in Australia, said in a press release. “It helps decide whether the progenitors go on to become T-cells or something else; if they become one type of T-cell or another type.” Interestingly, there are already drugs that target some of the pathways that PTPN2 regulates, which could lead to the use of existing drugs to treat some of these autoimmune diseases, including MS. “Understanding the mechanisms that govern early T-cell development and how these are altered in human disease may ultimately afford opportunities for novel treatments. This is very exciting,” said Florian Wiede, a post-doctoral candidate at Monash and first author of the study.

Ulcer Bacterium Might Play Role in MS, but More Studies Needed, Greek Researchers Say

Secondary progressive multiple sclerosis (SPMS) patients have larger quantities of certain antibodies to the stomach ulcer bacterium Helicobacter pylori than those with relapsing-remitting multiple sclerosis (RMSS), finds a Greek study which also showed that MS patients in general differ from healthy people in this aspect. Although researchers at the University of Thessaly think…

ACTRIMS 2018 Forum in San Diego to Showcase Latest Multiple Sclerosis Research

The Americas Committee for the Treatment and Research in Multiple Sclerosis, otherwise known as ACTRIMS, says its third annual ACTRIMS Forum will take place Feb. 1-3, 2018, at the Hilton San Diego Bayfront in San Diego, California. These forums bolster the ACTRIMS mission, which is to foster the careers of young researchers interested in MS by promoting mentor relationships with senior scientists, and giving promising investigators a chance to present their early research findings. ACTRIMS 2017 was a record-breaking year with over 800 people attending. Organizers say 1,000 people will attend this year's conference. The 2018 forum's theme is “Therapeutic Targets in MS: The Frontier and the Future of Disease Modifying Therapy.” ACTRIMS 2018 also features continuing medical education credits for attendees, as well as participation grants for applicable young investigators.

Human Gut Microbes May Help Suppress MS, New Research Suggests

A bacteria present in the gut, called Prevotella histicola, prevented multiple sclerosis from developing in a preclinical mouse model, found researchers at the Mayo Clinic in Rochester, Minnesota, along with colleagues at the University of Iowa. Current research suggests that alterations to the gut microbiome residing in human intestines may potentially trigger inflammatory diseases such as MS. In an attempt to identify which gut resident bacteria are capable of modulating immune responses, researchers studied cultured small pieces of intestine tissue extracted from biopsies of patients with celiac disease. The team then isolated three bacteria strains and found that one of species — P. histicola — had the capacity to suppress MS in a preclinical animal model of the disease. “This is an early discovery but an avenue that bears further study," Dr. Joseph Murray, a Mayo Clinic gastroenterologist and the study's lead author, said in a press release. "If we can use the microbes already in the human body to treat human disease beyond the gut itself, we may be onto a new era of medicine. We are talking about bugs as drugs." By investigating how P. histicola modulated immune responses to suppress MS, researchers found that bacteria decreased the expression of two pro-inflammatory cytokines – interferon-gamma and interleukin (IL)-17. Overall results show that P. histicola has immune modulatory activity and can suppress abnormal immune responses, which ultimately prevent autoimmunity. This supports the idea that maintaining a healthy microbial community within our intestines is a potential therapeutic strategy for MS. "Our work is a classic example of a bedside-to-bench and potentially back to bedside study. Recent MS microbiome studies have shown the lack of Prevotella genus in patients with the disease and an increase when patients were treated with disease-modifying drugs," said Ashutosh Mangalam, the study's first author and an assistant professor of pathology at University of Iowa's Carver College of Medicine. "And it's not just for MS, because this may have a similar modulating effect on other nervous system and autoimmune diseases."

Children and Teens with Multiple Sclerosis Consume Less Iron, Study Reports

Children with multiple sclerosis consume less iron, which may affect their immune and nervous systems, according to a study. Most MS cases occur between the ages of 20 and 40, but sometimes children under 18 develop it. Pediatric-onset MS, as it is called, is believed to account for 3 to 5 percent of cases that adults have now. Despite their low frequency, they are important because "the study of factors early in life which could affect their disease may provide important insight into the disease more generally," the researchers from the Network of Pediatric MS Centers wrote. One of the factors that could be important in the onset of MS is diet. But little has been known about how diet influences the risk and progression of the disease, particularly in pediatric MS. In a study funded by the National MS Society, researchers decided to investigate the association between diet and MS in children, according to a press release. The team recruited 312 MS patients 18 and younger from 16 children's hospitals in the United States, and 456 controls without MS. The participants, or their parents, answered a questionnaire dealing with the participants' medical history, their physical development, and whether they were exposed to potentially harmful environmental factors. The questionnaire also covered demographic information and race. Researchers used the Block Kids Food Screener questionnaire to obtain information about the participants' diets, including their intake of fiber, fat, carbohydrates, proteins, fruits, vegetables, dairy products, and iron. The analysis showed no meaningful link between the consumption of fiber, fat, carbohydrates, proteins, fruits, vegetables, and dairy products and children's development of MS. Children with the disease did have lower iron intake than the controls, however. Although in this exploratory study researchers didn’t look at whether there was a cause-and-effect relationship between iron and MS, the results suggested that children with the disease may be less likely to consume iron, a fact that warrants further investigation. Iron is a vital mineral for our body to function properly, and low iron intake may affect the immune and nervous systems. Future studies on the risk of children developing MS should "investigate the role of specific vitamins and minerals," the team said. They should also "investigate the influence of dietary factors on disease outcomes in already established" cases of MS.

Catching the Flu Can Trigger an MS Relapse by Activating Glial Cells, Study Suggests

Coming down with the flu can provoke relapses in multiple sclerosis patients by activating glial cells that surround and protect nerve cells. In a study in mice, scientists found that activated glial cells increase the levels of a chemical messenger in the brain that, in turn, triggers an immune reaction and, potentially, autoimmune attacks. The flu is caused by the human influenza virus and, despite being unpleasant, usually resolves itself within days. However, for people with MS and other neurological conditions, the flu can lead to disease relapse. Researchers at the University of Illinois investigated what happens in the brain of MS patients during upper-respiratory viral infections, such as the flu. "We know that when MS patients get upper respiratory infections, they're at risk for relapse, but how that happens is not completely understood," Andrew Steelman, an assistant professor at the university and the study's senior author, said in a press release. "A huge question is what causes relapse, and why immune cells all of a sudden want to go to the brain. Why don't they go to the toe?" The team used a mouse model characterized by autoimmune responses within the brain and spinal cord — the type of deregulated immune responses seen in MS patients. Researchers infected the animals with a version of human influenza virus adapted to mice, and looked at changes that occurred in the animal’s central nervous system. While the virus was never detected in the animals' brains, upon infection some of the mice developed MS-like symptoms. "If you look at a population of MS patients that have symptoms of upper respiratory disease, between 27 and 42 percent will relapse within the first week or two," Steelman said. "That's actually the same incidence and timeframe we saw in our infected mice, although we thought it would be much higher given that most of the immune cells in this mouse strain are capable of attacking the brain." The team then investigated how a peripheral influenza infection could contribute to disease onset. They infected a wild-type (normal) strain of mice with the flu virus and looked at alterations in the brain and spinal cord. Scientists found that infection increased the activation of glial cells in the mice's brains. Moreover, it induced infiltration of several immune cells — T-cells, monocytes and neutrophils — into the brain within eight hours of infection. Overall, these findings suggest that the chemokine CXCL5 plays a key role in mediating an autoimmune attack in MS, and might be explored for therapeutic potential.

Botulinum Toxin Treats MS Spasticity, But Support and Rehab Seen as Crucial to Long-term Use

Spasticity in multiple sclerosis patients can be eased through a combination of botulinum toxin type A (BoNT-A) injections and rehabilitation. However, caregiver support is required to keep patients on this treatment, according to results of a retrospective analysis. Spasticity, a muscle control disorder characterized by tight or stiff muscles, is a major MS symptom. The condition is significantly detrimental to patients’ quality of life, affecting their general mobility and balance. Several oral anti-spasticity drugs are available. However, “treatment of spasticity in MS is frequently challenging because of the complex clinical picture and the undesired effects associated with oral therapy, such as fatigue, dizziness, and hypotension,” the researchers wrote. Previous studies show that BoNT-A, a toxin that blocks nerve activity in muscles, is an effective therapy for the management of MS-related spasticity. The long-term effectiveness and persistence of BoNT-A use in patients with MS-related spasticity, however, remains poorly investigated. The research team in Italy proposed “to investigate the long-term persistence to treatment with BoNT-A for MS-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting.” In total, the researchers reviewed data from 185 patients, out of which 121 were considered in their final analysis. They observed that, at the end of the follow-up period, 44% of the patients in the analysis were still being treated with BoNT-A, but 56% had discontinued treatment. Overall, these results “confirm the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity,” the team concluded.

CrossFit Star Is Promoting Massaging Device That Myobuddy Says May Help MS Patients

Myobuddy Products has enlisted a rising fitness star to help it publicize its new Myobuddy Massager Pro, a massaging device that can help anyone from an elite athlete to a person with a muscle condition such as multiple sclerosis. Dakota Rager, who qualified for the national Reebok CrossFit Games competition, is a former Army diver who beat out more than 200,000 men in several regional competitions this year. CrossFit is a workout regimen aimed at improving the body's normal functional movements. The Massager Pro takes a multi-pronged massaging approach, including vibration, heat and percussion therapy, or applying tension to the body. The device's benefits including soothing sore muscles and helping relax tight fascia, or connective tissue surrounding muscles. Myobuddy started an MS Support Program in May to encourage MS patients to try massage therapy and to advance research on the approach. The company said some MS patients report that the Massage Pro helps them sleep better by alleviating their restless leg syndrome. They also report that it relieves muscle tension and fatigue, it added. Myobuddy's website includes information on how to use the Massage Pro for any muscle group. Those with questions can get answers by emailing [email protected] or calling (844) 696-2833. Rager (@ragerdakota), who at 5’4’’ and 169 lbs. is built like a fireplug, said he uses everything he can to give him an edge in competitions. If a massage therapy device is powerful enough to help MS patients, then it can help him, too, he has decided. "I really love the Myobuddy Massager, and have been using it throughout my training," he said in a press release. "It has the perfect combination of vibration and power and really goes deep to soothe my sore muscles and relax my tight ones after rigorous workouts. I highly recommend it for anyone who wants their muscles to feel and perform their very best." At only 25, Rager is already ranked as one of the top 100 CrossFit competitors worldwide. He was just one of 40 men to participate in the Reebok CrossFit Games in Madison, Wisconsin, Aug. 3-6. "We've had a lot of highly influential people in the sports and fitness world deliver organic endorsements for the Myobuddy, and we're extremely grateful for that," said Lillo Furca, Myobuddy's founder and CEO. "We've spent so much time and energy perfecting our massager to ensure that it delivers optimal results. The testimonies are a testament to our team and to our product." The company loves to "hear about how we're helping people who put their bodies in extreme situations on a regular basis," he added.

Restore Exosuit Could Help MS Patients Improve Their Walking Ability, Study Reports

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,…

Sunscreen Compounds Suppress Multiple Sclerosis Symptoms in Mice, Study Reports

Two compounds found in sunscreens suppressed multiple sclerosis symptoms in mice, a study shows. The substances, known as salate derivatives, belong to a class of compounds called nonsteroidal anti-inflammatory drugs. Evidence from the 1970s suggested that higher vitamin D levels from getting more sunlight could reduce the rate of MS. Subsequent studies indicated this was unlikely, however. Researchers who noticed that ultraviolet light suppresses MS in mice hypothesized that this could be the reason for the reduced prevalence of the disease in tropical areas. University of Wisconsin researchers wondered if sunscreen would prevent ultraviolet light from suppressing MS in mice. The team, led by Dr. Hector F. DeLuca, an emeritus professor in the university's Department of Biochemistry, chose six commercially available sunscreens, then exposed the mice to UV radiation. Confirming previous findings, they observed that UV radiation decreased the severity of MS. But, unexpectedly, they discovered that when mice were not receiving ultraviolet light, some of the sunblocks suppressed their MS for up to 30 days anyway. An analysis revealed that the salate derivatives homosalate and octisalate were the sunscreen components responsible for suppressing MS. The two are esters of salicylic acid, a common medication for acne, psoriasis, warts, and dandruff. Further analysis showed that homosalate was able to suppress MS by itself, but octisalate needed to be combined with homosalate to achieve significant results. The team also discovered that the salates' effectiveness depended on the dose. The more that homosalate was applied, the better the result, they said. The only adverse effect of homosalate and octisalate was temporary skin irritation. The study indicated that salate esters' ability to suppress MS is not due to their sunblocking ability per se, because some of the sunscreen brands that did a good job of blocking sunlight did not suppress the disease. Salate derivatives are well-known inhibitors of the enzyme cyclooxygenase, or COX. Because COX-2 has been found in MS lesions, salate derivatives might improve MS by suppressing COX, the researchers said. Overall, “salates may be useful in stopping the progression of MS, and may provide new insight into mechanisms of controlling autoimmune disease,” the researchers concluded.

Resistance Training Can Slow MS Patients’ Brain Shrinkage, Clinical Trial Indicates

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.

Long-term Tysabri Treatment Improved Quality of Life and Satisfaction with Therapy in Relapsing MS Patients, Study Finds

Long-term Tysabri (natalizumab) treatment of relapsing multiple sclerosis (RMS) improves physical and mental health and leads to greater satisfaction with therapy, new research shows. The study, ”Long-term natalizumab treatment is associated with sustained improvements in quality of life in patients with multiple sclerosis,” appeared in the journal…

Cell-Based Therapies in MS Remain Experimental, Expert Group Argues in Review Article

A group of experts recently concluded that clinical trials are the best way to explore whether cell-based therapies are viable options for treating multiple sclerosis. In a newly published article, MS researchers reviewed evidence on a range of cell therapies, including stem cell transplants and delivery or stimulation of various cell types. Clinical trials, the panel argued, would be the optimal way to examine which types of cells should be used, how they should be delivered, and the types and disease stages the treatments are suitable for. The article focused on four types of cell-based treatments: autologous stem cell transplants, mesenchymal and related stem cell transplants, use of drugs to manipulate stem cells in the body to boost their ability to repair, and transplants of oligodendrocyte progenitor cells to trigger new myelin production. Loss of the myelin that protects neurons is a hallmark of MS. Such treatments hold promise to attain what current disease-modifying therapies in MS have not: halting the disease without lifelong treatment that has potential side effects, and regenerating damaged tissue. In addition to reviewing the evidence surrounding cell-based treatments, the expert group focused on the availability of the treatment options outside of controlled trials. “Media attention has resulted in some cases of misrepresentation and exaggeration of therapeutic claims for cell-based therapies for multiple sclerosis and other diseases,” the team wrote. This has caused patients to seek the treatments — paying out-of-pocket — at unregulated clinics. The panel noted that several drugs in development, including opicinumab, are aimed at promoting remyelination. In addition, drugs that are already approved for other conditions might have remyelinating properties, and might be repurposed to treat MS. Although studies are ongoing, the panel noted that it is unclear if the drugs do promote remyelination. Despite ongoing research and — in some cases — clinical use of cell-based therapies for MS, these treatments should be considered experimental, the expert group concluded. They again underscored the importance of clinical trials in providing a controlled environment for patients wishing to have cell therapy, as well as a source of evidence for the feasibility of these approaches.

Columbia University Researchers Record Action of Receptor Linked to Neurodegenerative Diseases

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.”

Kezar Life Sciences Raises $50M to Advance Clinical Testing of Potential MS Treatment

Kezar Life Sciences announced that it is planning to move ahead with clinical testing of KZR-616, a potential treatment for multiple sclerosis (MS) and other autoimmune diseases and inflammatory disorders. The company recently concluded a Phase 1 safety study of the treatment, and raised $50 million in investment funding to support its development. KZR-616 is a first-in-class selective immunoproteasome inhibitor, meaning it works by blocking abnormal protein degradation. Cells eliminate proteins by sending them to a specialized cell compartment known as the proteasome. In immune cells, the proteasome is called immunoproteasome, and it regulates several selective inhibitors and participates in the regulation of the immune response associated with inflammatory diseases such as MS, rheumatoid arthritis, Crohn's disease, and lupus. "We are pleased with the results of our healthy volunteer study, and grateful for the support of such an excellent group of investors to finance our upcoming clinical trials," John Fowler, Kezar Life Sciences’ CEO, said in a news release. "The strong demand for this financing reflects growing excitement for the potential of immunoproteasome inhibition in treating autoimmune disorders and recognizes the clear leadership position enjoyed by Kezar." The Phase 1 trial enrolled 82 healthy subjects, who were assigned to receive either KZR-616 or placebo. In total, 61 volunteers were given KZR-616 as single or multiple doses at varying dose levels to identify the optimal dose for both tolerability and proteasome inhibition. Results will be presented at the American College of Rheumatology's Annual Meeting to be held in San Diego in November. "These initial clinical trial results demonstrate that KZR-616 is achieving the desired levels of immunoproteasome inhibition that correlate with anti-inflammatory activity seen in laboratory models,” said Christopher Kirk, PhD, company president and CSO. “By selectively targeting the immunoproteasome, we believe we can avoid the toxicities associated with dual proteasome inhibitors like Velcade and Kyprolis." The Series B financing round was led by Cormorant Asset Management and Morningside Venture and raised $50 million to support the development of KZR-616. Kezar announced it has the support of new investors, including Cowen Healthcare Investments, Pappas Ventures, Qiming Venture Partners, and Bay City Capital. "Cormorant is pleased to support Kezar as it enters an exciting series of patient studies, the first ever with a selective immunoproteasome inhibitor," said Bihua Chen, founder of Cormorant Asset Management. "While much work remains, I believe KZR-616 has the potential to be a transformative treatment in autoimmunity."