research

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

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

of the neurons.

The online multiple sclerosis community GeneFo will hold a webinar next week to discuss the latest research findings on how mitochondrial antioxidants may affect MS. The webinar, which will be open to patients who register, will start at 1 p.m. U.S. Eastern Standard Time on Thursday, Aug. 24. GeneFo…

I stood at the front door of my house and could only shake my head as I watched the backhoe digging a deep trench in my yard. A sewer line malfunction created a mess in my basement and it turned out to be a broken clay pipe in…

The risk of people with multiple sclerosis developing cancer is higher if they have used immunosuppressants than if they haven’t, according to a study that followed more than 1,000 patients for a decade. The findings indicate that the often discussed association between MS and cancer may stem from older types of…

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.

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…

I was surprised to see that a study of a potential MS drug labeled MD1003 is still accepting participants. It’s a study that I’d love to take part in, if only I was a few years younger. MD1003 is a high dose of biotin, a form of…

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.

University of California at San Francisco Recruiting MS Patients for Gut Bacteria Study Last year, a Harvard study reported significant differences between bacteria that MS patients have in their bellies and that found in those who don’t have MS. If that bacteria is treated, those MS-related changes might…

Atara Biotherapeutics recently published an update of the company’s quarterly financial results and operational highlights, including the advancement of its T-cell based immunotherapy strategies for multiple sclerosis (MS) and cancer. One of the investigational therapies featured in the report is ATA188, a potential treatment for MS.

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 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.

University of California medical school researchers are looking for multiple sclerosis patients who want to participate in an international study of the bacteria that live in our gut. The University of California at San Francisco team decided to study the gut microbiome after recent evidence suggested that it is critical in…

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.

Advancells says its stem cell-based therapy completely reversed multiple sclerosis (MS) in an Indian pilot trial with only one MS patient. The patient, Rahul Gupta, was diagnosed with MS seven years ago and has since suffered multiple relapses. His disease was progressing fast and he was quickly losing his ability…

Multiple sclerosis damages human brains, so MS researchers often study mice brains. How can multiple sclerosis be cured or prevented without studies of human brains? Researchers need the anatomical bequests of MS brains. Harvard Brain Tissue Resource Center Harvard University specifically collects and studies brains (and brain tissue),…

For the first time, scientists have shown they can correct gene mutations in human embryos — a breakthrough with implications for multiple sclerosis (MS) and several other diseases. This landmark study was a collaboration involving scientists at the Salk Institute in La Jolla, California; the Oregon Health & Science University in…

Resistance Training Can Slow MS Patients’ Brain Shrinkage, Clinical Trial Indicates Over the years, studies have shown the benefits of various types of exercise in improving MS symptoms. But here, Alice Melão reports about a small…

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,…

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.

I recently spent time at the annual meeting of the Drug Information Association (DIA), listening to presentations and talking with industry representatives about the multiple sclerosis community’s needs. DIA is a nonprofit association that has been around more than 50 years. Their primary interest is the development of healthcare…

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.

Twenty-four people have now received the multiple sclerosis and psoriasis therapy KY1005 in a Phase 1 clinical trial, according to its developer, Kymab. The Cambridge, England, company creates human antibody drugs for autoimmune diseases. The trial will focus on KY1005 as a psoriasis therapy, although its mechanism of action should work…

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…

Multiple sclerosis (MS) patients in the first year of diagnosis frequently suffer from depression, pre-morbid personality, self-perception issues and other psychological problems, an Italian study finds. Yet it is hard to predict the degree of symptoms since MS takes a different course in each individual. The study, “The first year after…

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.

If you’ve followed my writing, you already know I am committed to advancing patient-centered research and care. I am the lead patient representative and co-principal investigator for iConquerMS. One of the main goals of iConquerMS is to elevate the voice of people with MS into research. How do…

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.”