Posts tagged MS

July 31, 2012

Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by a type of immune cell in people with multiple sclerosis (MS) may play a role in the disease’s progression. The finding could lead to new targeted therapies for MS treatment.

B cells, said Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study, are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy.

In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges — the covering of the brain and spinal cord — that attract them. Once within the meninges or central nervous system, Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins but that damage oligodendrocytes, the cells that produce a protective substance called myelin.

The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and, in part, why they are attracted to the meninges and the nervous system.

The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons and bring messages from the brain to the muscles. The white parts of the brain are white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons. The myelin’s function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can “leak” and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons. 

The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, and after removing the cells from the culture collected material produced by the cells. After adding the material produced by the B cells, including the cells that produce myelin, to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.

"We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage," Lisak said.

The team is now applying for grants from several sources to conduct further studies to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.

Provided by Wayne State University

Source: medicalxpress.com

July 30, 2012

(Medical Xpress) — A new study by researchers at the Menzies Research Institute Tasmania (Menzies) suggests that one of the main treatments for multiple sclerosis (MS) may also increase the amount of vitamin D patients receive from sun exposure.

More people suffer with MS per capita in Tasmania than in any other state in Australia. There is currently no cure, but treatments are available to ease some of the symptoms.

This observational study published in the prestigious journal Neurology found that patients taking one of the most common treatments for MS, interferon-beta, had higher vitamin D levels than those not on this treatment or those using other forms of treatment for MS.

Around 60 per cent of MS patients with the relapsing-remitting form of MS are treated with interferon-beta. It is derived from a naturally-occurring component of the human immune system and has been found to reduce the frequency of relapse and other specific symptoms of MS.

Despite being a front-line treatment in MS, how interferon-beta actually works in MS is unclear, though it is thought to act by affecting the immune system.

The study used data from the MS Longitudinal Study, from 2002-2005, and this analysis used data from 178 persons with MS living in southern Tasmania.

Menzies researchers Dr. Niall Stewart and Dr. Steve Simpson, Jr. were co-first authors on the paper. Dr. Simpson says the findings suggest that part of the therapeutic effects of interferon-beta on relapse in MS may be through its effects on vitamin D, since vitamin D has the ability to reduce inflammatory pathways in the immune system.

“Not only did we find that persons taking interferon-beta had higher vitamin D levels than those not taking it, we also found that this increase in vitamin D was due to an enhancement of the association between sun and vitamin D, with persons on interferon-beta having nearly three-times as much vitamin D from similar amounts of sun exposure to those not taking interferon-beta,” Dr. Simpson said.

“We have previously shown persons with MS with higher vitamin D levels had lower numbers of relapses. In this analysis, however, we found that vitamin D was only associated with reduced risk of relapse among those using interferon-beta.

“Interestingly, the reciprocal was also true, with interferon-beta only associated with reduced risk of relapse among those with higher levels of vitamin D,” Dr. Simpson said.

Senior author, Professor Bruce Taylor, says the new findings have the potential to markedly affect clinical practice in the treatment of MS, but cautions that more research is required.

“This study adds to the growing body of research into MS, but before we can apply these findings to MS treatment practice, clinical trials must be done to prove these associations. Menzies is planning to undertake such a trial in the future,” Professor Taylor said.

“This study does provide further support for persons with MS to periodically have their vitamin D measured, particularly in winter, and if they are deficient, to seek the advice of their physician as to whether supplementation is appropriate for them.”

Provided by University of Tasmania

Source: medicalxpress.com

July 24, 2012

A new class of drug developed at Northwestern University Feinberg School of Medicine shows early promise of being a one-size-fits-all therapy for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and traumatic brain injury by reducing inflammation in the brain.

Northwestern has recently been issued patents to cover this new drug class and has licensed the commercial development to a biotech company that has recently completed the first human Phase 1 clinical trial for the drug.

The drugs in this class target a particular type of brain inflammation, which is a common denominator in these neurological diseases and in traumatic brain injury and stroke. This brain inflammation, also called neuroinflammation, is increasingly believed to play a major role in the progressive damage characteristic of these chronic diseases and brain injuries.

By addressing brain inflammation, the new class of drugs — represented by MW151 and MW189 — offers an entirely different therapeutic approach to Alzheimer’s than current ones being tested to prevent the development of beta amyloid plaques in the brain. The plaques are an indicator of the disease but not a proven cause.

A new preclinical study published today in the Journal of Neuroscience, reports that when one of the new Northwestern drugs is given to a mouse genetically engineered to develop Alzheimer’s, it prevents the development of the full-blown disease. The study, from Northwestern’s Feinberg School and the University of Kentucky, identifies the optimal therapeutic time window for administering the drug, which is taken orally and easily crosses the blood-brain barrier.

"This could become part of a collection of drugs you could use to prevent the development of Alzheimer’s," said D. Martin Watterson, a professor of molecular pharmacology and biological chemistry at the Feinberg School, whose lab developed the drug. He is a coauthor of the study.

In previous animal studies, the same drug reduced the neurological damage caused by closed-head traumatic brain injury and inhibited the development of a multiple sclerosis-like disease. In these diseases as well as in Alzheimer’s, the studies show the therapy time window is critical.

Read more …

July 23, 2012 By David Orenstein

(Medical Xpress) — This week the Journal of the American Medical Association published a study with unfortuate news for the millions of people who suffer from multiple sclerosis. In the large study, a therapy known as interferon beta failed to stave off the progression of the incurable disease. Albert Lo, associate professor of neurology and epidemiology, comments on what the study means for patients, why it was well-designed, and how a new effort to support research on the disease in Rhode Island could help.

The results of this study with nearly 2,700 participants showed that treatment with interferon beta, which is a major class of disease-modifying therapy for multiple sclerosis, did not prevent progression of disability, which is very disappointing from a therapeutic perspective. Currently, there is no cure for MS, and as a lifelong disorder of the nervous system, MS is characterized by episodic relapses of neurological injury such as weakness or blindness. While in most cases, there is a varying degree of recovery after relapses, over time, disability accumulates. The accumulation of deficits and the loss of physical and mental function is a major concern for people with MS and their clinicians.

Currently, there is no medication on the market that is directed explicitly for neuroprotection and the prevention of disability. Many had hoped that the interferons, along with the other disease-modifying agents (which were developed to reduce relapse rates) would also have a significant effect on protecting patients from MS disability.

Although the results from this study were not as we would have hoped, they reflect a marked improvement over prior studies which used known methodologic flaws. The new results from the Tremlett group point to the importance of the research methodology used (prospectively collected longitudinal study data) and a well-controlled design to generate the results – approaches that we are using in our own research at Brown University.

A number of the early studies examining the effect of interferons on disability primarily used patient sample groups of convenience for post-marketing studies. They indicated that interferons were in fact preventing disability. However, using samples of convenience inherently includes a number of biases and problems. Dr. Tremlett’s results were generated from a more systematic longitudinal study in which biases and shortcomings can be better addressed. Therefore, making conclusions and clinical decisions from the results is more reliable. These data both will help in making clinical decisions on treating MS patients during the later course of their disease, when there are virtually no relapses, and will help to point more urgently toward the clinical need of an agent to prevent disability.

Provided by Brown University

Source: medicalxpress.com

ScienceDaily (July 17, 2012) — A buildup of sodium in the brain detected by magnetic resonance imaging (MRI) may be a biomarker for the degeneration of nerve cells that occurs in patients with multiple sclerosis (MS), according to a new study published online in the journal Radiology.

The study found that patients with early-stage MS showed sodium accumulation in specific brain regions, while patients with more advanced disease showed sodium accumulation throughout the whole brain. Sodium buildup in motor areas of the brain correlated directly to the degree of disability seen in the advanced-stage patients.

"A major challenge with multiple sclerosis is providing patients with a prognosis of disease progression," said Patrick Cozzone, Ph.D., director emeritus of the Center for Magnetic Resonance in Biology and Medicine, a joint unit of National Center for Scientific Research (CNRS) and Aix-Marseille University in Marseille, France. "It’s very hard to predict the course of the disease."

In MS, the body’s immune system attacks the protective sheath (called myelin) that covers nerve cells, or neurons, in the brain and spinal cord. The scarring affects the neurons’ ability to conduct signals, causing neurological and physical disability. The type and severity of MS symptoms, as well as the progression of the disease, vary from one patient to another.

Dr. Cozzone, along with Wafaa Zaaraoui, Ph.D., research officer at CNRS, Jean-Philippe Ranjeva, Ph.D., professor in neuroscience at Aix-Marseille University and a European team of interdisciplinary researchers used 3 Tesla (3T) sodium MRI to study relapsing-remitting multiple sclerosis (RRMS), the most common form of the disease in which clearly defined attacks of worsening neurologic function are followed by periods of recovery. Sodium MRI produces images and information on the sodium content of cells in the body.

"We collaborated for two years with chemists and physicists to develop techniques to perform 3T sodium MRI on patients," Dr. Zaaraoui said. "To better understand this disease, we need to probe new molecules. The time has come for probing brain sodium concentrations."

Using specially developed hardware and software, the researchers conducted sodium MRI on 26 MS patients, including 14 with early-stage RRMS (less than five years in duration) and 12 with advanced disease (longer than five years), and 15 age- and sex-matched control participants.

In the early-stage RRMS patients, sodium MRI revealed abnormally high concentrations of sodium in specific brain regions, including the brainstem, cerebellum and temporal pole. In the advanced-stage RRMS patients, abnormally high sodium accumulation was widespread throughout the whole brain, including normal appearing brain tissue.

"In RRMS patients, the amount of sodium accumulation in gray matter associated with the motor system was directly correlated to the degree of patient disability," Dr. Zaaraoui said.

Current treatments for MS are only able to slow the progress of the disease. The use of sodium accumulation as a biomarker of neuron degeneration may assist pharmaceutical companies in developing and assessing potential treatments.

"Brain sodium MR imaging can help us to better understand the disease and to monitor the occurrence of neuronal injury in MS patients and possibly in patients with other brain disorders," Dr. Ranjeva said.

Source: Science Daily

ScienceDaily (July 12, 2012) — Diagnosing multiple sclerosis (MS) is a challenge even for experienced neurologists. This autoimmune disease has many symptoms and rarely presents a uniform clinical picture. New scientific findings on the immune response involved in MS could now help improve the diagnosis of this illness. Scientists analyzing the blood of MS patients have discovered antibodies that attack a specific potassium channel in the cell membrane. Potassium channels play an important role in transmitting impulses to muscle and nerve cells and it is exactly these processes that are inhibited in MS patients.

Right: The autoantibody can be seen binding to the membrane of glial cells in the MS serum. By comparison, the image on the left shows a blood sample from a patient with another neurological disease. (Credit: KKNMS)

The results are published in the current issue of the New England Journal of Medicine.

For the first time, scientists in Germany’s multiple sclerosis competence network have been able to identify an antibody that bonds with the potassium channel KIR4.1. “We found this autoantibody in almost half of the MS patients in our study,” explains Bernhard Hemmer, Professor of Neurology at the Klinikum rechts der Isar hospital at Technische Universität München (TUM). The biomarker was not present in healthy patients. The findings could therefore indicate that KIR4.1 is one of the targets of the autoimmune response in MS. Humans and animals without the KIR4.1 channel experience neurological failure and cannot coordinate their movements properly. Furthermore, their bodies do not create sufficient amounts of myelin, a layer of insulation that protects the nerve cells.

KIR4.1 is primarily present in the membrane of glial cells, which are responsible for controlling metabolism in the brain and forming myelin. The neurologists will now be conducting follow-up studies into how KIR4.1 antibodies influence the development of MS. This autoantibody is extremely rare in people with other neurological diseases, making it an important potential diagnostic marker for MS in the future. “This autoantibody could improve diagnosis of MS and help us differentiate it more clearly from other neurological diseases,” continues Hemmer. This will also be the focus of further research.

Source: Science Daily

July 11, 2012

A new study shows that taking part in a stress management program may help people with multiple sclerosis (MS) prevent new disease activity. The study is published in the July 11, 2012, online issue of Neurology, the medical journal of the American Academy of Neurology.

A weekly stress management program for patients with multiple sclerosis (M.S.) prevented the development of new brain lesions, a marker of the disease’s activity in the brain, according to new Northwestern Medicine research. Brain lesions in M.S. often precede flare-ups of symptoms such as loss of vision or use of limbs or pain.

"This is the first time counseling or psychotherapy has been shown to affect the development of new brain lesions," said David Mohr, principal investigator of the study and professor of preventive medicine at Northwestern University Feinberg School of Medicine. "In M.S., the prevention of new brain lesions is an important marker used to judge how effective medications are."

"The new finding is an important step and the strongest evidence we have to date that stress is involved in M.S.," Mohr added.

The results indicate that stress management therapy may be a useful adjunct treatment with drug therapy for M.S., but a larger clinical trial is needed to confirm this, Mohr said.

The study is published in the July 11, 2012 issue of Neurology, the medical journal of the American Academy of Neurology.

Mohr’s previous research showed a connection between psychological distress and the development of new brain lesions. Stress is one of many factors, he said, that influence whether the underlying M.S. disease processes escalate to the point of a new lesion or a relapse. Mohr has spent more than a decade studying the link between emotional distress, including a study on depression, and M.S.

For an event to be stressful, a person has to feel it is a threat to something important, and that he or she doesn’t have any control over it.

"We taught patients strategies to evaluate how much of a threat something truly is," Mohr said. "When people overestimate the threat of an event or underestimate their ability to manage it, we teach them how to evaluate their own thinking about the stress and how to challenge and change that thinking to a more realistic and helpful appraisal of the actual threat. That often leads to improved ability to manage stressful events."

Patients also were taught how to calm their physical reactions to stress through relaxation and meditation to cope with stressful events that couldn’t be avoided.

In the national clinical trial, 121 patients were randomized to receive stress management therapy for M.S. or be in a control group. Those in the therapy group received 16 sessions over a 24-week period during which they were taught coping skills to enhance their ability to prevent stressful events from occurring and to improve their capacity to manage their responses to stressful events that did arise. They also received a 24-week post-treatment follow-up. Two-thirds of the patients were women, who have a higher incidence of M.S.

MRI neuroimaging showed the stress management therapy reduced two types of new brain lesions common in multiple sclerosis.

The first type, gadolinium-enhancing brain lesions, indicates a breakdown of the blood-brain barrier, allowing the immune system access to attack and damage brain cells. Gadolinium is injected into an M.S. patient during the MRI and can be observed passing through the blood-brain barrier, if these types of lesions are present. These lesions may disappear over time or may leave more permanent damage in the brain.

The second type, a T2 brain lesion, is a more global marker of the effect of M.S. on the brain and is a more permanent lesion. These markers are commonly used in evaluating M.S. medications in Phase II trials. If the lesions are decreased, the implication is the drug is working.

Among patients who received stress management therapy, 55 percent had a new gadolinium-enhancing brain lesion during the treatment period, compared to 77 percent of those in the control group. Similarly, 43 percent receiving stress management therapy had a new T2 brain lesion during the treatment period, compared to 70 percent in the control group. The stress reduction prevented new lesions whether or not the patients were taking M.S. disease-modifying medications (e.g., beta-interferons or glatiramer acetate).

But the improvement in brain lesions didn’t last after the stress management program ended.

"This suggests that we will need to develop treatments that are more sustainable over longer periods of time," Mohr said. "It’s difficult for people to come in for treatment once a week over long periods of time, due both to cost and time constraints. We are looking at telemedicine programs that can be delivered via a computer or a smartphone to people in their environment at much lower costs than traditional therapy."

The study did not show a statistical difference in the rate of clinical M.S. symptoms, but Mohr said he didn’t expect one in such a small number of participants. The outcome goal of this trial was only to see if the stress reduction affected the brain lesions.

While the results are positive, Mohr said, it’s premature to make recommendations for patients regarding use of stress management therapy. “I don’t want to see patients decide not to take their medication and use this instead,” he emphasized.

Provided by American Academy of Neurology

Source: medicalxpress.com

July 2, 2012

The medication fingolimod reduced inflammatory lesion activity and reduced brain volume loss in patients with multiple sclerosis who participated in a two-year placebo-controlled clinical trial and were assessed by magnetic resonance imaging (MRI) measures, according to a report published Online First by Archives of Neurology.

Fingolimod is the first in a new class of drugs called the sphingosine 1-phosphate receptor (S1PR) modulators that was recently approved at 0.5 mg once daily for the treatment of relapsing multiple sclerosis (MS), a debilitating disease of the central nervous system, according to the study background.

The inflammatory pathology of MS can be seen by counting gadolinium (Gd)-enhancing lesions on T1-weighted images or new and enlarging T2 lesions on serial MRI scans. The extent of hyperintense areas on T2-weighted images provides an indication of the overall burden of disease, the study background explains.

The study by Ernst-Wilhelm Radue, M.D., of the Medical Image Analysis Center, University Hospital, Basel, Switzerland, and colleagues included 1,272 patients who were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial, a worldwide, multicenter effort. Patients received once-daily fingolimod capsules of 0.5 mg or 1.25 mg, or placebo.

"The anti-inflammatory effects of fingolimod therapy, as depicted by Gd-enhancing lesions and new/newly enlarged T2 lesions, were evident as early as 6 months after treatment initiation and were sustained over two years. Approximately half the patients receiving fingolimod therapy were free from any new inflammatory lesions throughout this 2-year study, compared with only 21 percent of patients receiving placebo," the authors comment.

Fingolimod, 0.5 mg (licensed dose), “significantly reduced” brain volume loss during the trial versus placebo, according to the study results. Brain atrophy is recognized as a useful way to monitor MS disease progression.

"These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution," the study concludes.

Provided by JAMA and Archives Journals

Source: medicalxpress.com