Posts tagged MS
Articles and news from the latest research reports.
OHSU researchers discover how enzyme may prevent nervous system repair in multiple sclerosis
Discovery could be ‘life-changer’ for millions with MS, stroke and other conditions that cause brain damage
Researchers at Oregon Health & Science University have discovered that blocking a certain enzyme in the brain can help repair the brain damage associated with multiple sclerosis and a range of other neurological disorders.
The discovery could have major implications for multiple sclerosis, complications from premature birth and other disorders and diseases caused by demyelination – a process where the insulation-like sheath surrounding nerve cells in the brain becomes damaged or destroyed. Demyelination disrupts the ability of nerve cells to communicate with each other, and produces a range of motor, sensory and cognitive problems in MS and other disorders.
The study was published this week in the online edition of the Annals of Neurology. The study was conducted by a team of researchers led by Larry Sherman, Ph.D., who is a professor of cell and development biology at OHSU and a senior scientist in the Division of Neuroscience at the Oregon National Primate Research Center.
"What this means is that we have identified a whole new target for drugs that might promote repair of the damaged brain in any disorder in which demyelination occurs," Sherman said. "Any kind of therapy that can promote remyelination could be an absolute life-changer for the millions of people suffering from MS and other related disorders."
New MS drug proves effective where others have failed
A drug which ‘reboots’ a person’s immune system has been shown to be an effective treatment for multiple sclerosis (MS) patients who have already failed to respond to the first drug with which they were treated (a ‘first-line’ therapy), as well as affected individuals who were previously untreated. The results of these two phase III clinical trials were published today in the journal The Lancet.
The new studies, sponsored by Genzyme (a Sanofi company) and Bayer Schering Pharma, showed that alemtuzumab significantly reduces the number of attacks (or relapses) experienced by people with MS compared to interferon beta-1a (known commercially as Rebif). This was seen both in patients who had not previously received any treatment (drug-naïve) and those who have continued to show disease activity whilst taking an existing treatment for MS.
Scientists deepen genetic understanding of MS
Five scientists, including two from Simon Fraser University, have discovered that 30 per cent of our likelihood of developing Multiple Sclerosis (MS) can be explained by 475,806 genetic variants in our genome. Genome-wide Association Studies (GWAS) commonly screen these variants, looking for genetic links to diseases.
Corey Watson, a recent SFU doctoral graduate in biology, his thesis supervisor SFU biologist Felix Breden and three scientists in the United Kingdom have just had their findings published online in Scientific Reports. It’s a sub-publication of the journal Nature.
An inflammatory disease of the central nervous system, MS is the most common neurological disorder among young adults. Canada has one of the highest MS rates in the world.
Watson and his colleagues recently helped quantify MS genetic susceptibility by taking a closer look at GWAS-identified variants in the major histocompatibility complex (MHC) region in 1,854 MS patients. The region has long been associated with MS susceptibility.
The MS patients’ variants were compared to those of 5,164 controls, people without MS.
They noted that eight percent of our 30-per-cent genetic susceptibility to MS is linked to small DNA variations on chromosome 6, which have also long been associated with MS susceptibility.
The MHC encodes proteins that facilitate communication between certain cells in the immune system. Outside of the MHC, a good majority of genetic susceptibility can’t be nailed down because current studies don’t allow for all variants in our genome to be captured.
“Much of the liability is unaccounted for because current research methods don’t enable us to fully interrogate our genome in the context of risk for MS or other diseases,” says Watson.
The researchers believe that one place to look for additional genetic causes of MS may be in genes that have variants that are rare in the population. “The importance of rare gene variants in MS has been illustrated in two recent studies,” notes Watson, now a postdoctoral researcher at the Mount Sinai School of Medicine in New York.
“But these variants, too, are generally poorly represented by genetic markers captured in GWAS, like the one our study was based on.”
(Source: sfu.ca)
MRI research sheds new light on nerve fibres in the brain
World-leading experts in Magnetic Resonance Imaging from The University of Nottingham’s Sir Peter Mansfield Magnetic Resonance Centre have made a key discovery which could give the medical world a new tool for the improved diagnosis and monitoring of neuro-degenerative diseases like multiple sclerosis.
The new study, published in the Proceedings of the National Academy of Science, reveals why images of the brain produced using the latest MRI techniques are so sensitive to the direction in which nerve fibres run.
The white matter of the brain is made up of billions of microscopic nerve fibres that pass information in the form of tiny electrical signals. To increase the speed at which these signals travel, each nerve fibre is encased by a sheath formed from a fatty substance, called myelin. Previous studies have shown that the appearance of white matter in magnetic resonance images depends on the angle between the nerve fibres and the direction of the very strong magnetic field used in an MRI scanner.
Using the Eye as a ‘Window Into the Brain’
An inexpensive, five-minute eye scan can accurately assess the amount of brain damage in people with the debilitating autoimmune disorder multiple sclerosis (MS), and offer clues about how quickly the disease is progressing, according to results of two Johns Hopkins studies.
“The eye is the window into the brain and by measuring how healthy the eye is, we can determine how healthy the rest of the brain is,” says Peter A. Calabresi, M.D., a professor of neurology at the Johns Hopkins University School of Medicine, and leader of the studies described in recent issues of The Lancet Neurology and the Archives of Neurology. “Eye scans are not that expensive, are really safe, and are widely used in ophthalmology, and now that we have evidence of their predictive value in MS, we think they are ready for prime time. We should be using this new quantitative tool to learn more about disease progression, including nerve damage and brain atrophy.”
Calabresi and his colleagues used optical coherence tomography (OCT) to scan nerves deep in the back of the eye, applying special software they co-developed that is capable of assessing previously immeasurable layers of the light-sensitive retinal tissue. The scan uses no harmful radiation and is one-tenth the cost of an MRI. The software will soon be widely available commercially.
Using a high-tech imaging process to measure the thickness of the eye’s retina may one day predict the progression of multiple sclerosis, a new study suggests.
The finding might lead to better ways to judge the effectiveness of treatments because different parts of the retina seem to indicate different aspects of the disease and the toll it takes on different parts of the brain, the researchers said.
The report was published online Oct. 1 in the Archives of Neurology.
Unique Genetic Marker Discovery May Help Predict Multiple Sclerosis Relapse
Scientists may be one step closer to predicting the uncertain course of relapsing-remitting multiple sclerosis (MS), a disease that can lay dormant for months or years, thanks to the discovery of a unique genetic marker. The marker, detailed by researchers in the August edition of The Journal of Immunology, is the first of its kind to be directly linked to MS.
The study, supported by funding from both the National Institutes of Health (NIH) and the Ohio State Center for Clinical and Translational Science (CCTS) was conducted by a team of scientists with The Ohio State University using blood samples from patients with MS, as well as mouse models. Researchers uncovered the molecule miR-29, while working to identify a biomarker in the blood that could indicate if a patient had an ongoing inflammatory response, such as MS.
“Our research was inspired by the knowledge gap that existed between microRNA and MS, as well as the unpredictable nature of MS,” said Kristen Smith, Ph.D., principal investigator, who received a “mentorship grant” to conduct the study alongside senior scientists at The Ohio State University Wexner Medical Center. “By identifying a unique marker associated with MS, we hope to inspire a relatively noninvasive test that could identify and predict the course of the disease, helping clinicians tailor therapies to disease progression.”
Source: newswise
Pill Found Promising in Treatment of M.S.
A new oral medication to treat patients in the early stages of has shown considerable promise in two clinical trials, researchers announced on Wednesday.
The medication is on track to become just the third oral drug available to M.S. patients, and potentially the safest and most effective, experts said. The second oral drug, called Aubagio, was approved just last week.
M.S. was virtually untreatable only two decades ago, but today nine “disease modifying” drugs are available for early-stage patients; a half-dozen more are in the late stages of development. Most patients in the early stage of the disease, a form called relapsing-remitting M.S., take drugs by injection.
The two new studies, published online in The New England Journal of Medicine, found that the drug BG-12, developed by Biogen Idec, reduced relapse rates in patients with relapsing M.S. by about 50 percent. The drug also significantly reduced the frequency of new brain lesions often associated with these attacks, and slowed the progression of disease compared with a placebo.
The studies were Phase 3 trials, a last step on the road to drug approval. The Food and Drug Administration is required to make a decision about the drug’s approval before the end of this year.
“This drug is clearly quite effective in managing disease and reducing disability, and the safety profile looks quite good,” said Timothy Coetzee, the chief research officer at the National Multiple Sclerosis Society, who was not involved in the studies.
is often a progressive disease in which the immune system damages neurons in the brain and spinal cord. A majority of people with M.S. have relapsing-remitting M.S., characterized by flare-ups that cause lesions in the brain to develop and neurological symptoms to emerge or worsen. Eventually, more than half of patients develop a progressive form of M.S., leading to permanent disabilities.
Interferons, the drugs most commonly used in relapsing M.S., reduce relapses by about 30 percent, and have not been shown to slow the progression of the disease and disability. The newly approved Aubagio also reduces relapses by about 30 percent, and it has the advantage of being an oral drug.
Two drugs that are substantially more effective, and Gilenya, come with serious risks including, in rare cases, death. They are used as second-line treatments when an initial approach fails, and patients require some monitoring.
In the new studies, called Define and Confirm, patients were randomized into two groups, taking 240 milligrams of BG-12 either twice or three times a day. Patients in a third group took a placebo. The combined results showed that the drug reduced the relapse rate by about 50 percent. There was minimal difference between the twice-daily and thrice-daily regimens.
Taking BG-12 twice a day reduced the number of new or newly enlarging brain lesions by 71 percent to 99 percent, depending on the type of lesion and the study. The Define study found a statistically significant 38 percent reduction in the progression to disability.
The most frequent side effects were a temporary flushing and warm feeling and gastrointestinal symptoms including nausea, , cramping and . Though both types of side effects were common, they tended to diminish after the first few weeks of use and were tolerated by most patients.
BG-12 is an anti-inflammatory that works by protecting nerves against injury. It is a fumaric acid, very similar to one widely used in Germany for the treatment of . “The safety track record is well known and appears to be very strong,” said Dr. Robert Fox, lead author of one of the two new studies and medical director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.
“It’s a bright day for M.S. patients, but there is a gray cloud in that we still don’t have anything for those with progressive M.S.,” he added.
MRI Findings Shed Light On Multiple Sclerosis
ScienceDaily (Aug. 21, 2012) — New magnetic resonance imaging (MRI) research shows that changes in brain blood flow associated with vein abnormalities are not specific for multiple sclerosis (MS) and do not contribute to its severity, despite what some researchers have speculated. Results of the research are published online in the journal Radiology.
"MRI allowed an accurate evaluation of cerebral blood flow that was crucial for our results," said Simone Marziali, M.D., from the Department of Diagnostic Imaging at the University of Rome Tor Vergata in Rome.
MS is a disease of the central nervous system in which the body’s immune system attacks the nerves. There are different types of MS, and symptoms and severity vary widely. Recent reports suggest a highly significant association between MS and chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by compromised blood flow in the veins that drain blood from the brain. This strong correlation has generated substantial attention from the scientific community and the media in recent years, raising the possibility that MS can be treated with endovascular procedures like stent placement. However, the role of brain blood flow alterations on MS patients is still unclear.
To investigate this further, Italian researchers compared brain blood flow in 39 MS patients and 26 healthy control participants. Twenty-five of the MS patients and 14 of the healthy controls were positive for CCSVI, based on Color-Doppler-Ultrasound (CDU) findings. The researchers used dynamic susceptibility contrast-enhanced (DSC) MRI to assess blood flow in the brains of the study groups. DSC MR imaging offers more accurate assessment of brain blood flow than that of CDU. MRI and CDU were used to assess two different anatomical structures.
While CCSVI-positive patients showed decreased cerebral blood flow and volume compared with their CCSVI-negative counterparts, there was no significant interaction between MS and CCSVI for any of the blood flow parameters. Furthermore, the researchers did not find any correlation between the cerebral blood flow and volume in the brain’s white matter and the severity of disability in MS patients.
The results suggest that CCSVI is not a pathological condition correlated with MS, according to Dr. Marziali, but probably just an epiphenomenon — an accessory process occurring in the course of a disease that is not necessarily related to the disease. This determination is important because, to date, studies of the prevalence of CCSVI in MS patients have provided inconclusive results.
"This study clearly demonstrates the important role of MRI in defining and understanding the causes of MS," Dr. Marziali said. "I believe that, in the future, it will be necessary to use powerful and advanced diagnostic tools to obtain a better understanding of this and other diseases still under study."
Source: Science Daily
Discovery of Immune Cells That Protect Against Multiple Sclerosis Offers Hope for New Treatment
ScienceDaily (Aug. 16, 2012) — In multiple sclerosis, the immune system attacks nerves in the brain and spinal cord, causing movement problems, muscle weakness and loss of vision. Immune cells called dendritic cells, which were previously thought to contribute to the onset and development of multiple sclerosis, actually protect against the disease in a mouse model, according to a study published by Cell Press in the August issue of the journal Immunity. These new insights change our fundamental understanding of the origins of multiple sclerosis and could lead to the development of more effective treatments for the disease.
"By transfusing dendritic cells into the blood, it may be possible to reduce autoimmunity," says senior study author Ari Waisman of University Medical Center of Johannes Gutenberg University Mainz. "Beyond multiple sclerosis, I can easily imagine that this approach could be applied to other autoimmune diseases, such as inflammatory bowel disease and psoriasis."
In an animal model of multiple sclerosis known as experimental autoimmune encephalomyelitis (EAE), immune cells called T cells trigger the disease after being activated by other immune cells called antigen-presenting cells (APCs). Dendritic cells are APCs capable of activating T cells, but it was not known whether dendritic cells are the APCs that induce EAE.
In the new study, Waisman and his team used genetic methods to deplete dendritic cells in mice. Unexpectedly, these mice were still susceptible to EAE and developed worse autoimmune responses and disease clinical scores, suggesting that dendritic cells are not required to induce EAE and other APCs stimulate T cells to trigger the disease. The researchers also found that dendritic cells reduce the responsiveness of T cells and lower susceptibility to EAE by increasing the expression of PD-1 receptors on T cells.
"Removing dendritic cells tips the balance toward T cell-mediated autoimmunity," says study author Nir Yogev of University Medical Center of Johannes Gutenberg University Mainz. "Our findings suggest that dendritic cells keep immunity under check, so transferring dendritic cells to patients with multiple sclerosis could cure defects in T cells and serve as an effective intervention for the disease."
Source: Science Daily