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After a decades-long search, scientists identify new genetic risk factors for multipl

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  • After a decades-long search, scientists identify new genetic risk factors for multipl

    This article IS for our friends here with MS.

    After a decades-long search, scientists identify new genetic risk factors for multiple sclerosis

    A pair of large-scale genetic studies supported by the National Institutes of Health has revealed two genes that influence the risk of getting multiple sclerosis (MS) – data sought since the discovery of the only other known MS susceptibility gene decades ago. The findings could shed new light on what causes MS – a puzzling mix of genes, environment and immunity – and on potential treatments for at least 350,000 Americans who have the disease.

    "These studies describe the first genes conclusively linked to MS in more than 20 years," said Ursula Utz, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH. “This breakthrough was made possible through persistence, an elegant search strategy, and genomic data and techniques that were not available until recently.”

    Both studies involved scanning DNA samples from more than 20,000 MS patients and unaffected individuals in the U.S. and Europe, and looking for single nucleotide polymorphisms (SNPs), which are single-letter variations in a gene's DNA code. Published simultaneously today in the New England Journal of Medicine and Nature Genetics, the studies demonstrate an association between MS and SNPs in two genes that encode interleukin receptors, proteins that serve as antennae on the surface of immune cells.

    Both studies were supported by NINDS and the National Multiple Sclerosis Society. The Nature Genetics study received additional support from the National Institute of General Medical Sciences (NIGMS). The NEJM study was also supported in part by the Penates Foundation.

    They were conducted by overlapping teams of scientists that used different gene-hunting strategies. One team, which scanned the entire human genome for MS risk factors, was co-led by David Hafler, M.D., Professor of Neurology at Harvard Medical School and Brigham and Women's Hospital in Boston, Stephen Hauser, M.D., Professor and Chair of Neurology at the University of California in San Francisco, and Alastair Compston, FRCP, Ph.D., Head of the Department of Clinical Neurosciences at the University of Cambridge, U.K. The other team, which focused their search on a set of genes they considered potential risk factors for MS, was co-led by Jonathan Haines, Ph.D., Director of the Center for Human Genetics Research at Vanderbilt University Medical Center in Nashville, Tenn. and Margaret A. Pericak-Vance, Ph.D., Director of the Miami Institute for Human Genomics at the University of Miami. Drs. Hauser, Compston, Haines and Pericak-Vance participated in both studies.

    MS typically causes limb weakness, vision loss and problems with coordination, and is the most common disabling neurological disorder of young adults. It's an autoimmune disease, occurring when the body's immune system mistakenly attacks a protective sheath around axons – the delicate cables that nerve cells use to connect with each other. Various immunosuppressant drugs can reduce symptoms and slow the disease's course, but most MS patients become increasingly disabled with time.

    The trigger for MS is unclear, though there's strong evidence for an interplay between genetic susceptibility and some type of environmental factor. Having a relative, especially an identical twin, with MS increases one's risk of developing the disease. In the mid-1970s, researchers discovered that human leukocyte antigens (HLA) account for some of this genetic susceptibility. HLAs are proteins displayed on all the body's cells to help the immune system distinguish self from non-self. A variant of the HLA-DRB1 gene, now widely accepted as the strongest genetic risk factor for MS, increases the likelihood of getting the disease up to four-fold.

    Still, HLA does not fully explain the genetic basis of MS; scientists have long realized that other genes must play a role that has been difficult to detect. Some studies have pointed to other HLA genes, but neither of the two genes reported today belong to that category. Both genes encode receptors on the surface of T cells – the immune system's mobile infantry – that enable the cells to respond to regulatory, secreted proteins called interleukins.

    "These are the first non-HLA genes to be unequivocally associated with MS," said Dr. Pericak-Vance. "They give us a new way of looking at the biology of the disease, and could be targets for therapeutic development."

    Both studies searched for a link between MS and SNPs that were previously identified by the HapMap, an NIH-supported project to catalog genetic differences in human populations.


  • #2
    I moved this post to the TM, MS, Non-traumatic SCI Forum, so that more people with MS will see it.

    For a long time, the genetic predisposition for MS was unclear. It was predominantly a disease of middle-age caucasian women that appeared to be localized to a geographical band that passed through Minnesota and Sweden. It is believed to be an autoimmune disease. Thus, the initial search for genes focused on certain genetic markers that tend to be associated with auto-immunity. In more recent years, the search has expanded to other factors and it appears to be associated with genes responsible for inflammation.



    • #3
      Risk genes for multiple sclerosis uncovered

      Updated Sun. Jul. 29 2007 6:08 PM ET News Staff

      Researchers have uncovered new genetic variations that appear to put one at increased risk for multiple sclerosis, in a discovery that's being called the first real progress on the genetics of MS in 30 years.

      The finding is the result of a huge, international research collaboration that sought the genetic basis of MS, an autoimmune disease of the central nervous system in which the body attacks and destroys the insulation along nerve fibres. It leads to symptoms ranging from mild muscle weakness to paralysis.

      It's long been suspected that MS arises from a combination of genetic and environmental factors. But the genetic source has remained mostly a mystery.

      Unlike diseases caused by a mutation in a single gene, MS appears to be among a list of complicated diseases in which a host of genetic variations contributes to a person's susceptibility, with each gene contributing only a small amount of risk.

      The only genetic link previously identified is in the major histocompatibility complex (MHC), a large cluster of genes responsible for many immune functions, including preventing the body's immune cells from attacking its own tissues.

      This latest research, which analyzed genomic information from 12,360 people, confirmed that link but went further.



      • #4
        This seems to be significant for the understanding of MS for finding treatments. Great.


        • #5
          Patients Treated With Betaferon® After First MS Attack Experienced Significant Delay

          Patients Treated With Betaferon® After First MS Attack Experienced
          Significant Delay In Disability Progression

          Main Category: Multiple Sclerosis News
          Article Date: 06 Aug 2007 - 0:00 PDT

          Patients treated with Betaferon® (interferon beta-1b) shortly after their first clinical MS event or "attack" showed a 40 percent lower risk of developing confirmed disability when compared to patients in whom treatment was delayed. The results which were fast-tracked and provide the first controlled evidence that delaying Betaferon® treatment has an effect on later accumulation of disability. No other MS therapy has demonstrated this effect in this early patient population.

          The BENEFIT study (BEtaferon in Newly Emerging multiple sclerosis For Initial Treatment), sponsored by Bayer Schering Pharma AG, compared Betaferon® treatment initiated after a first clinical event with delayed treatment. The study was conducted at 98 sites in 20 countries and included a total of 468 patients.

          In the study, investigators measured MS progression of patient disability using a validated, well-established scale called EDSS (Expanded Disability Status Scale).(1) Disability progression was defined as an increase in a patient's EDSS score by at least one point that was confirmed after six months. A confirmed increase by one point in the EDSS scale can be an important and robust predictor of permanent and severe disability later in the disease.(2)

          "This research has important implications for the way we treat MS, because for the first time, we have controlled data that irrefutably demonstrates the value of early intervention with effective treatment for patients," said Dr. Ludwig Kappos, Professor of Neurology and Clinical Neuroimmunology at the University of Basel, Switzerland, and lead investigator of the BENEFIT study. "These findings support the decision to actively treat patients at the first clinical sign of MS to delay the accumulation of disability."

          "The data from BENEFIT not only reinforces the evidence that treatment with Betaferon® after the first clinical attack reduces the risk of subsequent MS attacks, but is also the first to demonstrate an impact on disability progression." said David Bates, Professor of Clinical Neurology at the University of Newcastle upon Tyne, UK.

          Other highlights from the study include:

          -- Sensitivity analyses confirmed the robustness of the main findings.

          -- Development of neutralizing antibodies did not have an impact on disability-related or relapse-related outcomes in the trial. This confirms other published, peer reviewed research.(3)

          -- Betaferon® was safe and well-tolerated, with the reporting of adverse events (AEs) similar to those previously reported for the drug.(4)