Multiple Sclerosis Resource Centre
  • Home
  • About MS
  • MSRC Services
  • Get Involved
  • MS Research News
  • MSRC Groups
  • Useful Resources
  • Welcome To Josephs Court, MS Centre Of Excellence
  • Advertising
  • Best Bet Diet Group
  • E-Newsletter
  • Contact Us
  • Investor in People
    You are here : Home » MS Research News » New Discoveries » Biomarkers and MicroRNA

    Biomarkers and MicroRNA

    A A A
    [Print this page]

    Share |


    Biogen Idec in MS biomarker deal with Regulus

    MS Biomarkers Biogen Idec Inc. said that it will work with Regulus Therapeutics Inc. to identify microRNAs biomarkers in patients with multiple sclerosis.

    Biogen makes and sells several multiple sclerosis drugs including Avonex and Tysabri, and it is also developing BG-12, a pill that is seen as a promising treatment for the condition. The companies said Regulus believes the biomarkers may help identify the best patients for clinical trials of multiple sclerosis drugs, could be used to develop diagnostic tests and may help monitor the progression of the illness or relapses.

    MicroRNAs are small RNA molecules. RNA helps synthesize proteins in the body, and microRNA helps regulate the way genes work.

    Biogen will buy a stake in Regulus and will make upfront and potential milestone payments to the company. It did not disclose the size of the stake it is buying or the terms of any payments.

    Multiple sclerosis is a disease in which the immune system attacks healthy nerves. It can cause pain, numbness, slurred speech, impaired vision, muscle weakness, and neurological problems.

    Source: Bloomberg @2012 BLOOMBERG L.P (16/08/12)

    NextGen Sciences launches multiplex protein CSF biomarker assay for MS

    MS BiomarkersNextGen Group plc announced that its US-subsidiary NextGen Sciences Inc, a leader in biomarker discovery, measurement and qualification, has launched its csfmultiplesclerosis25 multiplex protein assay for multiple sclerosis. The assay simultaneously measures 25 human CSF (cerebrospinal fluid) proteins that are believed to have potential as biomarkers for the disease.

    Klaus Rosenau, Chairman and CEO of NextGen Group, commented, ‘The release of the csfmultiplesclerosis25 assay is another piece in our strategy of developing assays with protein content that is relevant to the CNS market we are striving to address. To ensure we continually deliver the high-quality assays that pharmaceutical, biotechnology and diagnostics companies need to inform their decision-making processes, NextGen Sciences is currently working to expand its CSF and Plasma discovery assays.’

    NextGen’s assay is based upon its multiple reaction monitoring (MRM) mass spectrometry platform and generates high quality reproducible data that companies can use in their drug and diagnostic development programmes. The MRM platform can be used to assay proteins and modified proteins for which there are no antibodies and can thus circumvent the limitations of current antibody based technologies.

    NextGen expects to develop further oncology and CNS disease-focused assay panels, both as proprietary products and with other companies, through partnerships and collaborations.

    Source: PR Web (28/07/11)

    MiRNAs possible biomarkers, treatment targets in MS

    Biomarkers for MSSeveral short, noncoding RNA molecules are associated with multiple sclerosis symptoms, perhaps in enough of a causal way to become therapeutic targets as well as biomarkers of disease, a researcher said here.

    These so-called micro RNA species, or miRNAs, may be critical in shifting immune responsiveness away from the benign Th2 profile, instead promoting pro-inflammatory Th1/Th17 responses, said Mireia Guerau de Arellano, PharmD, PhD, of Ohio State University in Columbus.

    Moreover, she told attendees at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) that their relative levels differ in relapsing-remitting and secondary progressive MS versus primary progressive disease, which otherwise have been difficult to distinguish biologically.

    Originally dismissed as "junk" in the human genome, miRNAs have since been found to be key regulators of gene expression, Guerau explained. In particular, they can silence protein-coding genes by inhibiting their translation or inducing destruction of messenger RNA molecules.

    Her research group went looking for miRNAs that were differentially expressed in CD4-positive T cells taken from 22 MS patients compared with 12 healthy controls.

    The patients included 12 with relapsing-remitting MS and five each with secondary or primary progressive disease.

    Most promising as biomarkers were miRNA species designated as miR-128, miR-340, and miR-27a-b.

    They all appear to control expression of a gene known as BMI-1. It has no relation to body mass index -- rather, it has previously been found to play a role in cellular housekeeping, as part of the ubiquitin-proteasome pathway.

    Previous research has indicated that BMI-1 is involved in some way with immune function, in that its deficiency impairs Th2 functioning and promotes Th1 responses, Guerau said.

    Oncology studies have also found that miR-128 actively represses BMI-1 function. So do miR-340 and miR-27a-b, she said.

    Expression of these latter miRNAs was significantly increased in the MS patients in her study relative to controls (P<0.05).

    Moreover, miR-340 in particular was significantly increased in the five patients with primary progressive MS relative to the controls (P=0.03).

    Transfecting the three miRNA species into mice made them more susceptible to experimental autoimmune encephalitis (EAE), the standard rodent model of MS, Guerau said.

    EAE severity scores were tripled in the miRNA-expressing mice compared with control animals.

    The potential for targeting these miRNAs with drugs was suggested by in vitro experiments, Guerau added. Treating naive CD4-positive T-cells from MS patients with specific inhibitors of these miRNAs partially restored a more Th2-like pattern of cytokine release, she said.

    Cells from the patients treated with the inhibitors showed about a 150% increase in interleukin-5 production, which is indicative of a Th2 response.

    "This shows potential for a therapeutic strategy, though there are still a lot more experiments needed in that regard," she said.

    The study was funded by the National Institute of Neurological Diseases and Stroke.

    Guerau and other researchers on the study declared they had no relevant financial interests.

    Source: MedPage Today © 2011 Everyday Health, Inc (06/06/11)

    New biomarkers allow for better diagnosis in MS

    Biomarkers in MSBiomarkers – mainly defined as surrogates serving as indicators for specific biological states – play an ever-increasing role in neuroscience and especially in the management of multiple sclerosis, scientists reported today at the 21st Meeting of the European Neurological Society (ENS) in Lisbon.

    In analyzing gene expression patterns, immunological changes and imaging abnormalities, physicians are now able to detect complex nervous diseases at an early stage, to better discern them from other types with similar clinical manifestations, to better foresee the outcome and to evaluate whether or not a patient responds adequately to a specific therapy.

    Biomarkers – surrogates which can be objectively measured and used as indicators for certain biological states, salutogenetic or pathogenetic processes or responses to pharmacological treatments – are of increasing importance in many areas of modern medicine, but especially so in neuroscience. Neurological diseases are most complex in nature, sometimes difficult to detect, and when relying only on clinical examinations, the effect or ineffectiveness of a therapy might become evident at a late stage.

    “Especially in multiple sclerosis (MS) and some related disorders such as optic neuritis and neuromyelitis optica, a number of new biomarkers now greatly help us to quickly and non-invasively confirm or reject a diagnosis, to anticipate the outcome and to check whether or not the chosen therapy is effective in this particular patient,” Prof. Massimo Filippi said today at the 21st Meeting of the European Neurological Society (ENS) in Lisbon. More than 3,200 neurological experts from around the world are currently discussing the latest developments in all areas of their specialty in the Portuguese capital.

    Massimo Filippi, Professor of Neurology, heads the Interdepartmental Research Programme “BrainMap” and the Neuroimaging Research Unit at the Scientific Institute and University “Vita-Salute”, Ospedale San Raffaele in Milan, Italy. “These are big steps towards therapies that can be speedily customised to a specific patient’s situation in these most burdensome types of diseases.”

    600.000 Europeans suffer from multiple sclerosis
    According to epidemiological studies, about 600.000 Europeans and 2.8 million persons worldwide suffer from MS, an inflammatory disease in which the myelin sheaths insulating the axons in the brain and the spinal cord are disintegrated, causing a wide array of clinical manifestations and leading to progressive physical and often cognitive disability. “The huge variability of symptoms, caused by the fact that MS can affect any part of the CNS, along with a lack of meaningful laboratory and paraclinical tests, led in the past to delayed or uncertain diagnoses,” Prof. Filippi added. “We are that much happier, therefore, that in recent years we could trace a remarkable number of biomarkers, allowing for an improved and quickened assessment of the disease and its progression.”

    Improved MS diagnosis and differential diagnosis
    Optic neuritis, an inflammation of the optic nerve potentially leading to a total loss of vision, can be an early sign for MS. “We now found out that the gene expression patterns in a whole blood analysis show significant differences in patients with optic neuritis compared to healthy controls, which can make an early detection of MS easier in the future,” Prof. Filippi said. Neuromyelitis optica (Devic’s disease) is characterised by inflammatory-demyelination and irreversible tissue loss concentrated in the spinal cord and the optic nerve. Seen by some as a subtype of “ordinary” MS and by others as a different, independent disease, it needs a different course of treatment than MS to achieve optimal results. “Neuromyelitis optica is characterised by an autoantibody profile distinct from that of MS, allowing for an improved differential diagnosis and an early start of the appropriate therapy,” Prof. Filippi added.

    Anticipating disease progression
    In MS, neurologists discern different phenotypes – including the relapsing-remitting, the primary progressive and the secondary progressive. Each of these has a different prognosis and may require different therapeutic approaches. As a consequence, there is an urgent need to define their pathophysiology. “Some of our new biomarkers make this job much easier,”

    Prof. Filippi explains. “For example, in so-called black holes, lesions with irreversible tissue damage, the patterns of the microglia activation are different in progressive MS as compared to the relapsing subtype. MR measures could also help characterizing the heterogeneous clinical phenotypes of the disease. In particular, patients with progressive MS have an over-recruitment of the cervical cord on functional MRI scans, which is more pronounced in secondary progressive than in primary progressive MS. In relapsing-remitting MS patients, diffusion tensor magnetic resonance imaging (DT-MRI) allows distinguishing the effects of specific tract damage on disability and cognitive impairment. Finally, in neuromyelitis optica, the presence of NMO-IgG (antibodies which destroy aquaporin-4, a protein serving as a water channel through the cell membrane) already in an early stage identifies patients with a worse prognosis.”

    Evaluating the response to treatment for MS
    Does an individual patient respond to treatment? This crucial question, too, can in many cases be answered with hitherto unknown efficacy due to new biomarkers and technology to measure them. “The longitudinal atrophy of the spinal cord, a potentially important indicator for disease evolution and treatment response, can now be evaluated more effortlessly by a new segmentation method,” Prof. Filippi continues. “Whether or not a patient responds to natalizumab, a synthetically created monoclonal antibody designed to block the destructive activity of white blood cells in MS, can be assessed by the amount of natalizumab binding to mononuclear cells found in peripheral blood. A marker for the chances that cladribine -- a drug targeted to inhibit the immune system overactive in MS patients --will actually reduce disease activity is the amount of activity measured before treatment: the more relapses, the more active brain lesions and the more progression in disability, the more effective the drug will probably be. The effectiveness of an immunosuppressive treatment in neuromyelitis optica can in turn be measured by the NMO-IgG (aquaporin-4-antibody) level: the lower it is, the better the response to therapy; the higher it is, the more probable are relapses.”

    A new area in MS assessment
    “With these discoveries, and many more possible biomarkers still under investigation, we are embarking on nothing less than a new area of CNS disease assessment,” Prof Filippi concludes. “Instead of being in the dark for months and years, or dependent on very expensive and burdening diagnostic tools, we increasingly understand an easier-to-read bio-language of the body. It is leading us on relatively simple paths to the right diagnosis and letting us watch the development of disease and/or treatment. We expect this shift in diagnostic paradigms to continue and to yield even more exciting possibilities within the next few years.”

    Source: European Hospital Copyright 1997-2009 by EUROPEAN HOSPITAL Verlags GmbH (31/05/11)

    Biogen Idec search for biomarkers in relapsing remitting MS

    Biogen LogoProtagen AG, a specialist in in-vitro diagnostics and GMP-compliant protein analysis announced today that they will be using the UNIarray® Platform to help discover biomarkers in relapsing remitting multiple sclerosis for Biogen Idec, Inc.

    Under the terms of the agreement, Protagen will apply its UNIarray® technology platform and expertise in autoantibody research to support retrospective analysis of samples from a Biogen Idec clinical trial for the purpose of finding predictive and response biomarkers associated with multiple sclerosis (MS) therapy.

    "There is an acute need to discover possible response and non-response biomarkers in MS using genomic and proteomic level markers," said Dr. Peter Schulz-Knappe, CSO of Protagen AG. "Autoantibody signatures play an increasingly important role as a technology platform that could be used to identify patients for optimized treatment efficacy and to monitor disease progression."

    "Pharmaceutical companies recognize more and more the importance of autoantibody signatures for drug development, and Protagen provides the right technology and unique expertise for collaborations in this area", said Dr. Stefan Müllner, CEO.

    Background: UNIarray® is a unique technology platform for the development of novel diagnostics based on indication specific autoantibody patterns in patient sera. These indication specific autoantibody patterns were already proven to be present in several autoimmune diseases, but also in cancer and neurodegenerative disorders. The systematic and indication-specific determination of autoantibody patterns will serve as a powerful basis to address hitherto unmet diagnostic needs. UNIarray® serves as platform for the development of product specific companion diagnostics and patient stratification tools for clinical studies.

    Source: Medical News Today © MediLexicon International Ltd 2004-2011 (30/03/11)

    Osteopontin concentrations are increased in cerebrospinal fluid during attacks of MS

    MS BiomarkersAbstract
    Background: The cytokine osteopontin (OPN) is a potential key player in the immunopathogenesis of multiple sclerosis (MS) and a candidate biomarker for disease activity.

    Objective: The objective of this study was to examine concentrations of OPN in the cerebrospinal fluid (CSF) across the clinical spectrum of MS.

    Methods: Our research consisted of a cross-sectional study of patients from two randomized, placebo-controlled trials. Concentrations of OPN and other blood and CSF markers were determined using an enzyme-linked immunosorbent assay (ELISA). Samples were obtained from untreated patients with exacerbation of clinically isolated syndrome (CIS) (n = 25) and relapsing-remitting MS (RRMS) (n = 41) of whom 48 participated in clinical trials, randomly allocated to treatment with placebo or methylprednisolone (MP) and undergoing repeated sampling after 3 weeks.

    Furthermore, we obtained CSF and blood samples from patients with primary progressive MS (PPMS, n = 9), secondary progressive MS (SPMS, n = 28) and other neurological disorders (OND, n = 44), and blood samples from 24 healthy subjects.

    Results: OPN concentrations were significantly increased in the CSF of patients with CIS (p = 0.02) and RRMS (p < 0.001) in exacerbation compared to patients with OND, and increased levels of OPN were associated with high values of other biomarkers of inflammation. At 3-week follow-up CSF OPN concentrations had decreased significantly from baseline regardless treatment with placebo or MP. Patients with PPMS had increased OPN levels in the CSF (p = 0.004) and high CSF levels of OPN were associated with high degrees of disability.

    Conclusions: OPN concentration in the CSF is a dynamic indicator of disease activity in RRMS, presumably reflecting ongoing inflammation. Increased CSF OPN concentrations in PPMS may indicate ongoing inflammation even in these patients.

    Börnsen L, Khademi M, Olsson T, Sørensen PS, Sellebjerg F.

    University of Copenhagen and Danish MS Research Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

    Source: Mult Scler. 2010 Oct 4. & Pubmed PMID: 20921238 (13/10/10)

    Consortium finds immune related MicroRNA changes in Multiple Sclerosis

    BloodA pair of microRNAs thought to regulate immune genes are found at lower levels in the blood of those with multiple sclerosis than in unaffected individuals, according to a study appearing online yesterday in PLoS ONE.

    Members of the Australia and New Zealand Multiple Sclerosis Genetics Consortium, known as ANZgene, used miRNA microarray profiling to compare miRNA patterns in blood samples from 59 individuals with MS and 37 unaffected controls. The researchers found lower expression of two miRNAs — miR-17 and miR-20a — in individuals with all three forms of MS tested in the study.

    Meanwhile, the team's follow-up experiments indicated that these miRNAs curb the expression of genes involved in activating T cells in the immune system — genes that also tend to be more highly expressed in MS blood samples. As such, they argued, the newly identified miRNAs may prove useful for those looking to come up with new MS treatments.

    "In all MS sub-types miR-17 and miR-20a were significantly under-expressed in MS," corresponding author Rodney Scott, a medical genetics researcher at the University of Newcastle in Australia, and his colleagues wrote. "The same T cell activation genes are also up-regulated in MS whole blood [messenger RNA], suggesting these miRNAs or their analogues may provide useful targets for new therapeutic approaches."

    MS is a neurodegenerative disease typically diagnosed in adults younger than 35 years old. Symptoms of the autoimmune condition may flare up intermittently and then subside in those who have a form of the disease known as relapsing remitting MS. In other cases, termed progressive MS, the condition advances slowly but continuously without this reprieve.

    Genetic studies have uncovered changes to both human leukocyte antigen (HLA) loci and non-HLA loci associated with MS risk. And a study of methylation patterns in MS discordant identical twins published this spring suggests epigenetics also have a role in disease risk.

    In an effort to find miRNAs involved in MS, ANZgene researchers used the Illumina Sentrix array matrix to assess 733 miRNA transcripts in 59 Caucasian individuals with MS who had not received T cell targeting treatment for the condition for three months or more. Among them: two-dozen individuals with relapsing remitting MS, 18 individuals with the primary progressive form of the disease, and 17 individuals with secondary progressive MS.

    They compared these miRNA profiles with those in 37 healthy, age-matched control individuals, identifying 26 miRNAs that are expressed at lower levels in blood samples from individuals with MS and a single miRNA expressed at higher levels in the patients.

    From the 26 up-regulated miRNAs in MS, the researchers narrowed in on two miRNAs with the most pronounced differences between cases and controls: miR-17 and miR-20a, miRNAs implicated in immune function.

    After verifying the differential expression of these miRNAs using real-time PCR, the team did a series of experiments in a Jurkat cell line generated from to a T cell lymphoma sample, looking at how knocking down or adding in the miRNAs affects gene expression.

    Their results suggest that miR-17 and miR-20a down-regulation is linked to enhanced messenger RNA levels for some of the same T cell related genes that get over-expressed in MS patient blood samples.

    Based on these findings, the researchers believe miR-17 and miR-20a might contribute to MS development. And regardless of whether the miRNAs directly contribute to the disease, they added, it may be possible to tweak immune related gene levels in MS by targeting these sorts of regulatory miRNAs.

    "Even if the miRNAs under-expressed in MS were not directly contributing to the immune cell signature observed in MS whole blood, the excessive T cell activation signature seen in MS and other autoimmune diseases suggest agents which can reduce this activity may be therapeutically beneficial," the team concluded.

    Source: Genomeweb © 2010 Genomeweb LLC. (13/08/10)

    New way of detecting Multiple Sclerosis biomarkers in the blood

    Blood SampleA breakthrough finding from Israel may lead to earlier diagnosis, more effective intervention, and perhaps even a cure for the autoimmune disease multiple sclerosis.

    Multiple sclerosis (MS) has devastated the lives of two million people around the world. The disease is more prevalent in cold climates and attacks twice as many women as men. There is currently no cure. Now, research from Israel may pave the way for a diagnosis before symptoms appear and debilitation sets in. Earlier diagnosis of the disease will allow earlier medical intervention - and perhaps even lead to a cure.

    Prof. Anat Achiron of Tel Aviv University's Faculty of Medicine and director of the Multiple Sclerosis Center at Sheba Medical Center has uncovered a new way of detecting MS biomarkers in the blood. Her findings were published in the journal Neurobiology of Disease and are expected to pave the way for a diagnosis of MS before symptoms can appear, allowing for earlier treatment.

    Commenting on the study, Helen Yates, Multiple Sclerosis Resource Centre Chief Executive said, “Any test that can identify MS very early on in the disease course is very welcome.  One of the most important factors in MS is to treat, by whatever chosen method, as early as possible to prevent further damage within the CNS.  MSRC welcomes this research and hopes that the test progresses to become a standard part of the diagnostic toolkit."

    MS attacks the central nervous system and eventually renders most patients disabled. The National MS Society estimates that there are currently about 400,000 cases in the US. In Israel there are an estimated 5,000 cases, according to the Israel Multiple Sclerosis Society.

    "We are not yet able to treat people with MS to prevent the onset of the disease but knowledge is power," Achiron says. "Every time we meet a new patient exhibiting symptoms of MS, we must ask ourselves how long this has been going on. We can diagnose MS by brain MRI, but we've never been able to know how 'fresh' the disease is," she says.

    Identifying MS a decade before symptoms appear

    If doctors can predict the onset of MS early enough, intervention therapies that stave off MS symptoms might be able to be used sooner.

    "We theorized that if we looked at the gene expression signature of blood cells in healthy people, we could look for possible biological markers that characterize those who subsequently developed MS," Achiron explains.

    Examining blood samples of 20 19-year-old Israelis who were inducted into the army as healthy soldiers, and the nine of them who later developed MS, Achiron and her team at Sheba were able to use a "high throughput analysis" with more than 12,000 gene transcripts expressions. The screening compared similarities and differences in the blood of those who developed MS and those who did not, eventually establishing biological markers.

    "Those who will develop MS will show a different blood signature from those who will not," states Achiron. "When we compared the gene expression signatures, we saw a similar pattern of the same working biological processes."

    These early genetic markers may now be used to test for MS up to nine years before healthy young adults start developing symptoms. And because MS is thought to have a genetic component and a tendency to be found in siblings, Achiron foresees that the biomarkers will be used as a tool for brothers and sisters of patients.

    Clues for early intervention

    Why test in advance of a cure? "The idea is that we'll know more about the genetics of MS through this new discovery, with the hope that early intervention therapies may be more effective, and help advance medicine toward a cure," responds Achiron. This new insight into who will develop MS in the future is a first step on the path of finding a cure to the disease.

    By the time a person notices symptoms, significant and irreversible nerve damage has already occurred. MS is classified as an autoimmune disease that afflicts the brain and spinal cord. Symptoms vary, because the location and severity of each attack can be different, and until now, there has been no way of knowing who it will strike.

    The disease causes the body's immune system's T cells to mistakenly regard the myelin sheath around our body's neurons as foreign, so the immune system starts attacking the sheath, causing neurons to short circuit.

    Source: Israel21c  and MSRC(14/06/10)

    Chronix study supports use of circulating DNA in monitoring Multiple Sclerosis disease status

    Cronix Biomedical LogoChronix Biomedical today announced that a study published in the current online edition of the Journal of Molecular Diagnostics supports the use of the firm's technology in monitoring the clinical status of chronic disease.

    The San Jose, Calif.-based firm said that the study is the first to show that its approach, which identifies disease-specific genetic fingerprints based on circulating DNA released into the bloodstream by damaged and dying cells, can be used for such monitoring purposes.

    In the study, researchers used Chronix's techniques to identify genomic fingerprints in the bloodstream of 28 multiple sclerosis patients known to have relapsing or stable disease. They compared these patients with 50 healthy volunteers.

    According to Chronix, the researchers were able to distinguish the MS patients from the healthy volunteers. They also were able to use the circulating DNA fingerprints to differentiate periods of active disease attacks from the stable periods of disease remission characterizing relapsing-remitting MS, which affects about 85 percent of MS patients, the firm said.

    "These positive data further validate the premise underlying the Chronix approach, showing that the many genetic anomalies associated with active and stable relapsing-remitting MS can be detected by analyzing DNA fragments circulating in the blood serum," Mario Clerici, chair of immunology in the Department of Biomedical Sciences and Technologies at the University of Milano in Italy, and a co-author of the study, said in a statement. "The prognostic value achieved in this study supports the ability of this new approach to help manage relapsing-remitting multiple sclerosis, potentially offering clinicians a new tool to easily assess which MS treatment options are most effective for their patients, as well as providing critical information that will facilitate development of the next generation of MS therapeutics."

    Source: Genomeweb © 2010 Genomeweb LLC (08/04/10)

    Two kinds of Multiple Sclerosis, two different responses to beta-interferon, Stanford study shows

    Multiple Sclerosis Beta - interferonSTANFORD, Calif. — There may be two distinct versions of multiple sclerosis, a study in both animal models and human blood samples suggests. What’s more, a patient’s responsiveness to the most popular first-line drug for this episodic and all-too-often recurring autoimmune condition seems to depend on which version that patient has.

    If these findings are confirmed in larger human studies and by other laboratories, people with multiple sclerosis might someday be able to take a simple blood test to see whether they are likely to respond to treatment with the standard multiple-sclerosis therapy, said senior study author Lawrence Steinman, MD, the George A. Zimmerman Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine.

    Public health may benefit, too, Steinman said, as the cost savings from being able to predict in advance which patients will benefit from beta-interferon, a costly bioengineered drug whose global sales come to some $4 billion a year, could be considerable.

    Beta-interferon’s overall efficacy is only fair, he said, with perhaps half of all multiple-sclerosis patients experiencing an average one-third reduction in recurrences. Plus, its discomfiting side effects — flulike symptoms — can make compliance an issue for patients, especially given the drug’s iffy efficacy.

    In a study to be published online March 28 in Nature Medicine, Steinman and his colleagues used an established animal model of multiple sclerosis called experimental autoimmune encephalitis, or EAE, which they induced by injecting the animals with myelin in a way that caused the immune system to inappropriately attack the animals’ own myelin nerve-cell coatings.

    Many nerve cells in mammalian brains and peripheral tissues must convey electrochemical impulses over great distances, and quickly. Long, wirelike projections that transmit these cells’ signals to other nerve or muscle cells are coated by myelin, a natural substance whose insulating properties sustain the impulses’ strength and increase their speed.

    Multiple sclerosis is triggered when, for reasons that are not yet clear, immune cells called T cells attack the myelin sheathing, causing symptoms including paralysis and blindness. The condition affects 400,000 people in the United States, according to the National Multiple Sclerosis Society.

    A few years ago while still a PhD student at the University of Alabama, the study’s first author, Robert Axtell, had shown that, as in people with multiple sclerosis, beta-interferon can reverse paralysis in mice with EAE. But it turns out that EAE can be induced by two different autoimmune pathways, characterized by different patterns of secretion by T cells.

    Like nerve cells, immune cells also communicate with one another across long distances, but they accomplish this through various chemicals called cytokines that they secrete into the blood. Immune cells on the receiving end of a cytokine “signal” may respond quite differently, depending on the particular type of cytokine to which they are exposed. Two cytokines called gamma-interferon and IL-17, for example, tend to induce the kinds of inflammatory immune-system arousal that can trigger multiple sclerosis.

    Axtell (now a postdoctoral scholar in Steinman’s lab), Steinman and their colleagues were able to induce two superficially similar forms of EAE in mice by directing the myelin-attacking T cells to predominantly secrete either gamma-interferon or IL-17, respectively. The researchers found that beta-interferon improved the condition of animals whose EAE had been induced by gamma-interferon-secreting T cells, but exacerbated symptoms in those whose EAE had been induced by IL-17-secreting T cells.

    Intrigued, the investigators turned to humans. Another postdoctoral scholar in the Steinman lab, Brigit deJong, MD, the study’s second author, had previously been involved in research in Amsterdam in which multiple-sclerosis patients were treated with beta-interferon and meticulously followed up. The Stanford group obtained blood samples taken from 26 of these patients both before and about two years after the initiation of treatment. Without knowing which samples came from patients who had responded well or poorly to beta-interferon treatment, they went about measuring IL-17 levels in those samples.

    Eventually, patients’ follow-up histories were revealed to the researchers and their measured IL-17 levels were paired with their post-treatment progress. A clear pattern emerged. Measurements of a particular variety of IL-17, called IL-17F, clustered at either very high or very low levels in individual patients’ blood. Those with very low detectable blood levels of IL-17F responded well to beta-interferon treatment, experiencing no relapses or instances of required steroids (to quickly shut down a malfunctioning immune system). But patients with very high IL-17F levels — about one out of three subjects — responded poorly by the same criteria. In fact, said Steinman, there is some evidence that beta-interferon actually worsened these patients’ conditions.

    Steinman cautioned that the results need to be confirmed in larger patient groups, in his lab as well as in others. But, he said, “I think this has the potential to transform the way we take care of people with multiple sclerosis.” He said a simple, already available blood test could spare many patients the inconvenience and side effects — and spare the health-care system the expense — of a drug that most likely won’t do any good. “The other side of the coin is that beta-interferon, if it’s given only to those who are predisposed to respond to it, could turn out to be a far better drug than we ever imagined.”

    Although Steinman and his colleagues do not stand to benefit in any direct way from this work, Stanford University’s Office of Technology Licensing has filed a patent application on the use of the blood test. Earlier work by Steinman, proceeding from animal models to clinical trials, led to the development of another blockbuster multiple-sclerosis drug, natalizumab, marketed under the trade name Tysabri.

    Helen Yates, Chief Executive, MSRC said, “This piece of research potentially offers a very new light on MS particularly in relation to the use of the Beta Interferon drugs.  It has long been a problem understanding why some people with MS seem to do quite well on these drugs whilst others fair badly.  Some people have such a dreadful experience on the Beta Interferon group that they come off the drug but with no explanation as to why this is. 

    To be able to test, pre-treatment, for the likelihood of the drug having a positive impact will not only save money on drug prescriptions but more importantly, will mean that the person with MS will know, from the outset if there is any value in starting this particular course of treatment.

    MSRC welcomes further study into this very interesting area.”

    Several other scientists from Stanford and elsewhere co-authored the Nature Medicine study, which was funded by the National Multiple Sclerosis Society. Axtell’s former PhD advisor, Chander Raman, PhD, of the University of Alabama-Birmingham’s Department of Medicine, shares senior authorship with Steinman. More information about Stanford’s Department of Neurology and Neurological Sciences, which supported the work, is available at http://neurology.stanford.edu/.

    Nature Medicine Article - T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis 

    Source: The Stanford University School of Medicine & MSRC (28/03/10)

    Possible early diagnosis method for Multiple Sclerosis discovered

    Blood BiomarkersResearchers at the Multiple Sclerosis Unit of the Donostia Hospital in Donostia-San Sebastian, in collaboration with a bioinformatics team (Sistemas Inteligentes) from the University of the Basque Country, have published a study in the journal Public Library of Science (PLoS One) that for the first time links the expression patterns of molecules called microARN with multiple sclerosis.

    This is a discovery that may lead to a new diagnostic tool, and a European patent has already been applied for. Multiple sclerosis is a neurodegenerative disease of the central nervous system, and its origin is still unknown.

    The disease appears in the form of attacks and there is no known cure. There are an estimated 75 cases per 100,000 of the population (in the Basque Country there may be more than 2,000 sufferers), it is particularly prevalent in young adults and, after epilepsy, it is the second most common neurological disease.

    The research looked at 384 microARNs in three groups of people; patients who suffered severe attacks of multiple sclerosis, patients who had the illness but who did not suffer attacks, and healthy individuals (the control group).

    "We found that the combination of 10 different microARNs can help to detect the illness. It is a great step forward", explained David Otaegui, the director of the study, "as it opens the door to the possibility of developing new therapeutic targets and perhaps a blood biomarker that will complement current diagnostic tools."

    The biomarker would be able to tell which people have developed the illness and when they suffer or have suffered an attack. In this way, effective prevention of the disease could be carried out and available treatments could be applied earlier, making them more effective. In addition, the study allows researchers to try to understand the disease. "If we understand it better, we can improve treatment."

    The Basque Foundation for Health Innovation and Research (BIOEF), which manages the intellectual and industrial copyright of research going on in the Basque public health system, has filed an application for a patent to protect these results and the development of a potential commercial application for these findings, which will come in the form of diagnosis kits for the illness in three to five years time”.

    The research is the result of two years work of the laboratory of Dr. Otaegui (with the help of doctorate students Haritz Irizar and Maider Muñoz), of clinical research directed by the neurologist Javier Olascoaga in collaboration with the neurologist Adolfo López de Munain and the immunologist Álvaro Prada, all in Donostia Hospital, and also the researchers Iñaki Inza and José Antonio Lozano from the Artificial Intelligence group of the University of the Basque Country. The research group is currently replicating the study in a larger group of people to validate the conclusions they have obtained, and results of this study are expected to be in by the middle of 2010.

    Source: EITB news - Copywrite EITB 2009 (26/10/09)

    Genetic clue may predict Multiple Sclerosis severity

    Blood SamplesA newly identified biomarker may be linked to the severity of multiple sclerosis and may one day help with diagnosis and treatment of the often frustrating and unpredictable disease.

    Multiple sclerosis is a disease of the brain and spinal cord that affects more than 400,000 Americans. MS is believed to be an autoimmune disease because the body’s immune system attacks the protective myelin sheath around nerve fibres. This results in problems with nerve messages being conducted to and from the brain.

    In a new study published in Nature Immunology, researchers identified short RNA molecules, known as microRNAs, that were linked to multiple sclerosis symptoms in mice, depending on their level of activity or expression. The researchers found that when expression of the microRNA called miR-326 was silenced, MS severity in mice was mild. When the microRNA expression was increased, disease severity was severe.

    The researchers note that microRNAs have been linked to regulation of autoimmunity in mouse studies, but details about the specific microRNAs involved in autoimmune disease are unclear.

    Predicting Multiple Sclerosis Severity

    Researcher Changsheng Du of the Shanghai Institute for Biological Sciences at the Chinese Academy of Sciences in Shanghai, China, and colleagues found that the microRNA called miR-326 is also associated with severity of multiple sclerosis in humans.

    They found that miR-326 expression was much higher in the immune cells of MS patients compared to patients with a different neurological disease that affects myelin. The biomarker appears to correlate with the severity of multiple sclerosis by affecting the production of certain inflammatory proteins.

    Researchers say learning how to manipulate these microRNA molecules in humans may help lead to better treatments for the disease. It may also serve as a marker to help diagnose the disease, monitor response to treatment, and predict prognosis.

    Source: Web MD ©2005-2009 WebMD, LLC. All rights reserved.(20/10/09)

    MicroRNA biomarkers provide reliable MS diagnosis from blood samples

    BiomarkersData published in BMC Cancer and PLoS ONE show that febit's tailored biochips enable the identification of miRNA biomarker signatures for diagnosing lung cancer and multiple sclerosis from blood samples

    Data published in BMC Cancer and PLoS ONE show that microRNA (miRNA) biomarkers provide reliable and highly differentiated diagnosis from blood samples for lung cancer and multiple sclerosis. The invasive and often painful procedure of collecting patient tissue samples may become obsolete in the coming years.

    A research group led by Prof. Eckart Meese at the University of Saarland (Germany) investigated the performance of an innovative miRNA analysis method developed by febit biomed gmbh in patients with non-small cell lung cancer (NSCLC) and in patients suffering from multiple sclerosis.  

    Using febit's Geniom RT Analyzer, biomarker sets of 24 (lung cancer) and 48 (multiple sclerosis) miRNAs have been identified. They provide accurate discrimination of patients with NSCLC or multiple sclerosis from healthy individuals with 95 percent accuracy.


    "We can rapidly incorporate any desired miRNA by using febit's highly flexible biochip technology," said Prof. Meese. "The automated microarray analysis ensures high sample throughput in short periods of time. We can use small amounts of easily accessible biological specimens such as blood. This allows
    us to conduct large-scale, comprehensive studies."

    Peer Staehler, febit's CSO, said: "MiRNA biomarkers have a broad diagnostic potential. Since miRNA patterns are influenced by disease progression or the response to a treatment, this type of biomarker analysis provides additional information on the course, prognosis and appropriate therapy that the treatment can be tailored to each patient."

    febit's technology will enable scientists to perform successful and efficient SNP (single nucleotide polymorphism) screening in large-scale studies, searching for certain point mutations in many patient samples per sequencing run instead of sequencing one sample at a time.  

    About febit

    febit develops, produces and markets flexible automated solutions for enabling biochip applications in Life Sciences. febit's  product portfolio includes various instruments, optimized assays and genomic services, complemented by bioinformatics software and consulting.

    For its main applications - HybSelect, febit's innovative DNA capture method for Next-Generation-Sequencing and transcriptome profiling, especially miRNA Biomarkers - the highly advanced microfluidics of the patented Geniom Biochip offers the highest degree of automation, flexibility and efficiency available

    Source: febit holding gmbh (13/10/09)

    Blood test may predict the course of Multiple Sclerosis

    MS Blood Test?Scientists have discovered a blood test that could predict the course of multiple sclerosis (MS), or even indicate who is likely to develop the condition after a first MS-like attack.

    The results of the study suggest that differing antibody levels produced in response to the common virus Epstein Barr Virus (EBV), may predict the course of MS.

    If proven in further studies, this would be the first credible biological indicator, or biomarker, identified for MS that could predict disability progression from a simple blood test.

    The innovative work was carried out at the Institute of Neurology, UCL and the Institute of Cell and Molecular Biology, Barts and The London and was funded by the MS Society.

    It is hoped the findings will aid the development of better ways to predict who goes on to develop MS after initial MS-like symptoms and help in identifying more effective therapies for the 100,000 people living with MS in the UK.

    The paper's lead author, Clinical Research Fellow Dr Rachel Farrell, said: "All the participants in our study had previous history of infection with EBV, which has been shown in other studies and is not surprising given that a large majority of the adult population is infected with EBV.

    "What was surprising is that the levels of a molecule in the blood called anti-EBNA-1 IgG, induced by the virus, were associated with the activity of MS.

    "The results of this work show that those participants who had new areas of MS damage in the brain also had high levels of the anti-EBNA-1 IgG molecule in their blood.

    "In addition, participants with higher levels of EBNA-1 in the bloodstream were more likely to have an increase over time in the disability associated with MS."

    The researchers received funding of nearly £35,000 from the MS Society's Innovation Research grant scheme and looked at 100 participants, 50 of whom had a single MS-like attack but no diagnosis of MS, 25 people with relapsing-remitting MS and 25 with primary progressive MS.

    They tested participants for evidence of EBV infection in the blood and also looked for anti-EBNA-1 IgG and other EBV induced antibodies. MRI brain scans of each participant were taken over a five year period and the scientists also measured disability progression.

    The authors of the study, published in the journal Neurology, concluded that anti-EBNA-1 IgG is a potential biomarker in MS that might be useful in predicting disability and progression.

    They added that the work needed to be validated in larger studies and in combination with other as yet unidentified biomarkers.

    Dr Susan Kohlhaas, Research Communications Officer at the MS Society said, "We're delighted that such an interesting study has produced these valuable results that will give scientists a new avenue of MS research to explore.

    "Identifying biomarkers of MS is a key area of research and this work is a stepping stone on the path to mapping out the course of the condition and potentially determining prognosis.

    "People with MS find the uncertainty of what the future holds very daunting so more knowledge about what might lie in store could be a big help."

    Source PR Newsire (31/08/09)

    RNA-based biomarkers for Multiple Sclerosis to be studied

    Biomarker research

    Source MDx announced a partnership with Brigham and Women's Hospital in Boston to examine RNA-based biomarkers in multiple sclerosis (MS) patients and healthy control participants unaffected by the disease. The goal of the study is to identify diagnostic markers and to determine markers of active disease (relapses) or stable disease, along with response markers for currently available MS therapies.

    The study will utilize Source MDx's patented gene expression profiling for the identification and monitoring of MS. The lead investigators for the study are Phil De Jager, M.D., Ph.D., Assistant Professor in the Department of Neurology at Brigham and Women's Hospital and the Harvard Medical School/Partners Healthcare Center for Genetics & Genomics, and David Hafler, M.D., Director of Molecular Immunology at Brigham and Women's Hospital and Professor of Neurology of Harvard Medical School.

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system and is the most common disabling neurological condition to affect young adults. The progression of the disease is unpredictable and varies from person to person. For many, the disease entails periods of complete or partial remission interspersed with an exacerbation of MS (also known as a relapse, attack or flare) that causes new symptoms. Others experience slowly worsening neurologic function from the beginning with no distinct relapses or remissions. The determination of the stage of the disease is imprecise using currently available technologies, whereas gene expression profiles may provide clear guidance on the progression of the disease and response to treatment.

    "Our objective is to evaluate RNA-based markers in the broader context of each patient's genetics, protein markers, family history and clinical information in order to determine markers that can help in making a diagnosis of MS and prognosticate on drug response in MS," commented Dr. De Jager. "By doing so, we hope to be better able to identify markers that could lead to improved diagnostic tools, therapies or treatment regimen."

    The study is part of ongoing research conducted by Dr. De Jager and Dr. Hafler along with colleagues at the International Multiple Sclerosis Genetics Consortium (IMSGC) and the Partners Healthcare MS Center. The IMSGC has completed the largest replicated whole genome scan for MS to date. Its data identifying two new genetic variations associated with MS was published in the New England Journal of Medicine ("Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study," August 30, 2007). This large, whole genome association study has evaluated over 12,000 subjects and represents seminal work in the MS field.

    Source MDx has been conducting research related to MS since 1999 and has patented the use of gene expression data to allow more accurate identification, monitoring and treatment of MS. Gene expression biomarkers independently identified and patented by Source MDx through the company's precise and calibrated approach have subsequently been shown to be genetically linked to MS susceptibility according to the work completed by Drs. De Jager and Hafler.

    "We look forward to working with Brigham and Women's Hospital and furthering our ongoing research in biomarkers associated with inflammatory disease in general and MS specifically," commented Karl Wassmann, chief executive officer, Source MDx. "We believe this research will ultimately lead to improved, more targeted treatments for patients."

    Although little is known about the pathogenesis of MS, it is well recognized to cluster in families and it is clear that genetic factors have an important influence over an individual's risk of developing the disease.

    Source: centerdaily.com Copyright 2008 The Centre Daily Times (05/11/08)

    Possible fast-track Multiple Sclerosis test unveiled by Yorkshire team

    Immune Cells

    Testing for diseases including cancer and multiple sclerosis could soon be as simple as using a pregnancy test kit, Yorkshire scientists claim today.

    A team from Leeds University has developed technology that uses antibodies to detect biomarkers – molecules in the human body which are often a marker for disease – much faster than current testing methods.

    The technology could be used by doctors for more accurate referral to consultants and in hospitals for rapid diagnosis.

    Tests have shown that a wide range of substances can be detected using the approach including biomarkers in prostate and ovarian cancer, stroke, multiple sclerosis, heart disease and fungal infections.

    The team also believes that the technology could even be versatile enough to test for diseases such as tuberculosis and HIV.

    It has been developed through a £2.2m European collaboration of researchers and commercial firms.

    Paul Millner from the university's faculty of biological sciences said almost any biomarker could be detected faster, cheaper and more easily using the technology.

    "We believe this to be the next generation diagnostic testing," he said.

    Currently blood and urine are tested using a method developed in the 1970s, which takes on average two hours to complete, is costly and can only be performed by highly-trained staff.

    The Leeds team are confident their new technology, which provides results in 15 minutes or less, could be developed into an easy-to-use device the size of a mobile phone into which different sensor chips could be inserted depending on the disease being tested.

    Professor Séamus Higson, dean of the faculty of medicine and biosciences at Cranfield University in Bedfordshire, one of the partners in the programme, said: "The speed of response this technology offers will be of great benefit to early diagnosis and treatment of many diseases and will permit testing in environments such as GP surgeries."

    A spinout company has been set up to bring the technology to the market.

    Tim Gibson of Leeds University, who has managed the programme, said there were other potential uses for the technology.

    "We've also shown it can be used in environmental applications, for example to test for herbicides or pesticides in water and antibiotics in milk," he added.

    Source: Yorkshire Post ©2008 Johnston Press Digital Publishing (01/10/08)

    Potential new therapeutic target for progressive Multiple Sclerosis indentified

    Mayo Clinic Logo

    A new Mayo Clinic study has found that two particular enzymes were elevated in patients with progressive multiple sclerosis (MS). The levels of these enzymes also were associated with the patients' levels of disability. These findings give researchers new hope in developing a therapy for patients with progressive MS.

    This study was presented at the American Neurological Association annual meeting in Salt Lake City on Sept. 23, 2008.

    Mayo Clinic provides care for nearly 2,500 patients with MS each year. MS is a disease of the central nervous system that includes the brain, spinal cord and nerves. MS is called a demyelinating disease because it results from damage to myelin, the insulating covering of nerves. It occurs most commonly in those between the ages of 20 and 40, and is the most frequent neurological disorder in young adults in North America and Europe. Approximately 330,000 people in the United States have MS. Symptoms include loss of muscle coordination, strength, vision, balance and cognition. In patients with progressive MS, these symptoms do not decrease in intensity, while patients with relapsing/remitting MS may experience partial or total recovery from symptoms.

    "The current MS therapies are most effective for relapsing/remitting MS, with fewer options for patients with progressive MS," says Isobel Scarisbrick, Ph.D., a Mayo Clinic neuroscientist and a lead author of this study. "It's also sometimes difficult to diagnose which type of MS a patient has, and it's important to treat these patients differently."

    To help distinguish between the types of MS and identify a therapeutic target for progressive MS, Dr. Scarisbrick and a team of Mayo Clinic researchers studied five different Kallikreins, or secreted enzymes, in patients with MS. The team tested the level of each Kallikrein in the blood of 35 patients with MS and 62 healthy patients. They found that Kallikrein 1 and Kallikrein 6 were significantly elevated in patients with progressive MS. Additionally, the higher the level of Kallikrein 1, the higher the patient's level of disability, which was measured by expanded disability status score. The Mayo Clinic team also looked at the effects of these enzymes on neurons isolated from the brains of mice and found that both Kallikrein 1 and Kallikrein 6 caused significant loss of neurons and injury to axons.

    "We will continue to study how Kallikrein 1 and Kallikrein 6, either separately or together, play roles in neuron injury and how it occurs in patients with progressive MS," says Dr. Scarisbrick. "Eventually, we hope to determine a way to target these enzymes with therapies that will benefit patients with progressive MS."

    Other members of the Mayo Clinic research team included Rachel Linbo, D.P.T.; Alexander Vandell, Pharm.D.; Nadya Larson, Ph.D.; B. Mark Keegan, M.D.; Diane Sneve; Claudia Lucchinetti, M.D.; and Moses Rodriguez, M.D. Other contributors included Eleftherios Diamandis, M.D., Ph.D. of Mount Sinai Hospital, New York, NY, and Sachiko Blaber and Michael Blaber, Ph.D., both of Florida State University, Panama City, FL.

    This study was funded by a grant from the National Multiple Sclerosis Society and the Craig H. Neilsen Foundation.

    Source: The Mayo Clinic (24/09/08)

    Cerebrospinal fluid proteome profile in multiple sclerosis

    Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment.

    Using the two-dimensional difference gel electrophoresis (2-D-DIGE) technology for comparative analysis, we compared CSF samples from patients with MS of the relapse-remitting type (RRMS, n and from patients with clinically isolated syndrome (CIS,n suggestive of a first demyelinating attack with neurologically normal controls.

    Protein spots that showed more than two-fold difference between patients and controls were selected for further analysis with MALDI-TOF mass spectrometry. Immunoblot analysis was performed to confirm the validity of individual candidate proteins. In RRMS, we identified 1 up-regulated and 10 down-regulated proteins. In CIS, 2 up-regulated and 11 down-regulated proteins were identified. One of these proteins (Apolipoprotein A1) was confirmed by immunoblot.

    Though the pathophysiological role of these proteins still remains to be elucidated in detail and further validation is needed, these findings may have a relevant impact on the identification of disease-specific markers.

    Source: Multiple Sclerosis 2007; 13: 840—849.(21/09/07)

    Italian-German Research Team Discovers Cellular Marker for Multiple Sclerosis

    In their search for the cellular and molecular causes of multiple sclerosis, an Italian-German research team has identified a subgroup of protective immune cells (suppressor cells) which are strikingly reduced in number in patients with this nervous system disorder. These suppressor cells are characterised by a specific surface marker, called CD39, and degrade ATP, an energy carrier released from damaged tissues. By this means, suppressor cells appear to be able to curb inflammation occurring in the central nervous system in the course of the disease.

    With CD39, Dr. Giovanna Borsellino (Laboratory for Neuroimmunology of the Fondazione Santa Lucia in Rome, Italy) in collaboration with Dr. Olaf Rötzschke and Dr. Kirsten Falk (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch, Germany) have for the first time identified a cellular marker whose disappearance can be directly correlated to the manifestation of multiple sclerosis. As they report in the American journal Blood (Vol. 110, No. 4, pp. 1225-32, 2007), reduced numbers of CD39 suppressor cells may be indicative for the disease. At present, multiple sclerosis is diagnosed by testing for antibodies in the cerebrospinal fluid or by performing MRI scans of the brain. The future will show whether this new finding can also be useful for the development of a new therapy.

    In multiple sclerosis, misdirected "auto-reactive" immune cells destroy the isolating myelin sheath surrounding the nerve fibres, disrupting the transmission of neuron signals. In healthy individuals, a special group of suppressor cells, also referred to as regulatory T cells, is one of the means how the body's defense-system keeps such amok-running immune cells in check.

    Only recently, researchers in *Heidelberg could show that the thymic production of regulatory T cells is impaired in patients with Multiple Sclerosis. In addition, research groups in Europe and the USA have revealed that genetic variations of two genes related to regulatory T cells can increase the risk of developing multiple sclerosis. The genes CD25 and CD127 encode the interleukin receptors 7 and 2, which regulate the activation of immune cells.

    *Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression.

    Source: uni-protocolle (15/08/07)

    BG Medicine and Multiple Sclerosis Research Center of New York Announce Collaboration on Biomarker Discovery for MS Disease Activity and Drug Response
    The Multiple Sclerosis Research Center of New York (MSRCNY) and BG Medicine today announced that the two organisations have entered into an agreement to collaborate on research in the area of multiple sclerosis. Initial projects under the agreement are expected to be the discovery of biomarkers of MS disease activity and biomarkers of efficacy and safety for a currently marketed MS drug treatment.

    MS is the most common neurological disease in the world in people of young age, affecting approximately 350,000 people in the US alone. The MSRCNY and BG Medicine collaboration will focus on the discovery and development of novel blood tests that can be used in routine management of MS patients. The wide availability of such tests could have a profound impact on the management of MS by increasing the ability of physicians to measure their patient's level of disease activity and improve pharmaceutical treatment.

    "Two hallmarks of MS are its heterogeneity -- how its manifestations differ between patients -- and its variability -- how it can change over time through remissions and exacerbations," said Saud A. Sadiq, M.D., director of MSRCNY and of the International Multiple Sclerosis Management Practice (IMSMP), a combined research and clinical centre located in midtown Manhattan. "If we can supplement our clinical observations with blood tests that tell us about the level of disease activity or drug effectiveness or safety, we will advance our management of this common serious condition beyond anything imaginable at this time."

    Biomarkers of disease activity can also play an important role in advancing drug discovery and development by allowing researchers to perform much smaller, shorter, and lower-cost studies in comparison to studies that rely on conventional clinical observations. Additionally, MS-related biomarkers may help to better elucidate the mechanisms involved in MS susceptibility and progression.

    "We are at the dawn of a new era in medicine in which we can use biomarkers to understand and measure diseases early and thus treat the actual disease process," said Pieter Muntendam, MD, President and CEO of BG Medicine. "This partnership with MSRCNY will leverage their high level of scientific expertise in MS and their access to patients to facilitate the discovery and development of MS biomarkers for the improved clinical management of the disease."

    Under the terms of the agreement between the parties, MSRCNY will provide project expertise, certain analytical capabilities, and clinical patient samples for use by BG Medicine for the discovery, development, validation, and subsequent commercialisation of clinical biomarkers in exchange for certain payments from BG Medicine.

    About BG Medicine

    BG Medicine is a life sciences company focused on the discovery, development and commercialisation of novel molecular diagnostics to improve patient care and reduce healthcare costs. BG Medicine discovers biomarkers and develops its diagnostic product candidates using its proprietary, versatile, and scalable technology platform, which integrates the precise measurement and analysis of thousands of proteins, metabolites, and nucleic acids derived from bodily fluids or tissues. This approach to biomarker discovery allows the company to pursue the most promising opportunities unconstrained by biology or specimen type. BG Medicine is leveraging its technology platform in multiple biomarker initiatives and collaborations with leading clinical research centres, major pharmaceutical companies, premier healthcare companies, and the US Food and Drug Administration.

    About MSRCNY

    The Multiple Sclerosis Research Center of New York is a non-profit independent medical research organisation dedicated to finding the cause and a cure for multiple sclerosis. MSRCNY focuses on translational research, bringing findings quickly from the laboratory into clinical application to treat symptoms of MS and to halt or reverse damage caused by the disease. Current research includes studies in genetics, immune mechanisms, virology, protein biology, and stem cell repair and regeneration. MSRCNY also serves an educational function, providing advanced training for medical professionals interested in entering or expanding their work in MS, and sponsoring conferences and symposia for professionals and the public.

    Source: Business Wire (16/05/07)

    © Multiple Sclerosis Resource Centre

    Related Items
    Abnormal Liver Tests and MS
    AlphaB-crystallin
    Aluminium and Multiple Sclerosis
    Antagonist compounds
    Antibodies, B Cells,T-Cell Activation, Immune Response
    Apolipoprotein D
    Bacteria & MS
    Blood tests
    Bone Marrow Cells and MS Treatment
    Bowmann-Birk Inhibitor Concentrate (BBIC)
    Brain Atrophy, Lesion Loads, White and Grey Matter
    Brain Inflammation
    Brain Iron Deposits
    Calcium Binding Proteins
    Cerebro-Spinal Fluid & Spinal Cord
    Chronic Cerebrospinal Venous Insufficiency (CCSVI)
    CRMP-2
    CXCL1, 7, 12
    Cytokines & Chemokines
    Dendritic Cells
    Estrogen Receptors
    Fibrinogen, Mac-1 and Microglia
    HDL
    HERV-Fc1
    Histamine and MS
    Hormones And MS Research
    Immunoglobulins
    Infections and Multiple Sclerosis Relapses
    Interleukin-1beta
    JAK-STAT inhibitors
    Kallikrein 6
    Lipids & MS
    Lymphoid Tissue Inducer (LTi) Cells
    Medical Imaging
    Mycoplasmas And Bacteria
    N-acetylglucosamine (GlcNAc) & Glucosamine
    Natural Interferon Beta
    Natural Killer Cells
    Nerve and Brain Cell Research
    Neurosteroids
    Olig 1 Gene Discovery
    Oligodendrocytes and Astrocytes
    Pesticides and Multiple Sclerosis
    PKC-theta
    Plasma Exchange
    Potential Viral Causes of MS
    Proteomics
    Recombinant Human Erythropoietin
    Regeneration Research
    RNA and RNAi
    Synthetic Small Molecules
    Technology
    Tetanus Vaccine and Possible MS Protection
    Tetramers
    The Blood Brain Barrier
    Tremors And MS
    Uric Acid
    Urinary Problems
    Vascular Function And MS
    Vision and MS


    Did you find this information useful? Would you like to comment on this page? Let us know what you think! We welcome all comments and feedback on any aspect of our website - please click here to contact us.