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Researchers at Lund University have published new research findings on the role of the intestinal barrier in the autoimmune disease multiple sclerosis (MS).
Within medical science, it is not known for certain how MS develops or why the body's immune system attacks cells in the central nervous system. Inflammation develops for an unknown reason, which hinders transport of neural impulses. This can produce various physical and mental symptoms, including a loss of sensation, motor difficulties, blurred vision, dizziness and tiredness.
The present study investigates whether the function of the intestines is also attacked in MS. The results, obtained from a disease model of MS in mice, shows inflammation and changes in the barrier function of the intestines early in the course of the disease. The study has been published in the scientific journal PLOS ONE.
"We know that the permeability of the intestines to harmful substances is raised in inflammatory bowel diseases such as Crohn's disease and ulcerous colitis, as well as in some other autoimmune diseases such as type 1 diabetes. The condition is called 'leaky gut syndrome'. Our studies indicate a leaky gut and increased inflammation in the intestinal mucous membrane and related lymphoid tissue before clinical symptoms of MS are discernible. It also appears that the inflammation increases as the disease develops", said Shahram Lavasani, one of the authors of the study.
Dr Lavasani and his colleagues at Lund University have previously shown that probiotic bacteria could give a certain amount of protection against MS. They therefore wondered whether the intestinal barrier is affected and decided to investigate inflammatory cells and processes in the intestine. The hypothesis was tested in a research project in collaboration with Professor Björn Weström, doctoral student Mehrnaz Nouri and reader Anders Bredberg.
"To our surprise, we saw structural changes in the mucous membrane of the small intestine and an increase in inflammatory T-cells, known as Th1 and Th17. At the same time, we saw a reduction in immunosuppressive cells, known as regulatory T-cells. These changes are often linked to inflammatory bowel diseases, and biologically active molecules produced by Th1 and Th17 are believed to be behind this damage to the intestines."
Neuroinflammatory processes in MS are believed to lead to damage and leakage in the blood-brain barrier that protects the central nervous system and regulates the transport of cells. The researchers have now observed similar damage in the intestinal barrier, especially to the 'tight junctions' that bind the cells together in the mucous membrane of the intestine, and have demonstrated that these are connected to disease-specific T-cells.
"In most cases, we don't know what triggers autoimmune diseases, but we know that pathogenic cells frequent and disrupt the intestines. A leaky gut enables harmful bacteria and toxic substances in the body to enter the intestine, which creates even more inflammation. Our findings provide support for the idea that a damaged intestinal barrier can prevent the body ending an autoimmune reaction in the normal manner, leading to a chronic disease such as MS", said Dr Lavasani.
Shahram Lavasani and his colleagues believe that future drugs to treat this type of disease should perhaps not only focus on the central nervous system, but also on the intestines by repairing and restoring the intestinal barrier.
"In the long run, we hope that our findings will lead to better understanding of what actually happens in the development of MS. Looking even further to the future, we hope for the development of a better treatment that aims at the intestinal barrier as a new therapeutic target."
The research group is now studying other inflammatory parameters in the gut that could affect the development of MS. Their aim is to draw up treatment methods that can heal the mucous membrane in the intestine in the hope of preventing the development of the disease. Some of this work forms part of Mehrnaz Nouri's thesis, which will be defended later in the year.
The Johns Hopkins University
School of Medicine and the Institute for Johns Hopkins Nursing, in
cooperation with Medical Logix, LLC, are pleased to offer this new
educational program certified for CME and CNE credit, at no charge to
presented by the Johns Hopkins University School of Medicine and the
for Johns Hopkins Nursing
Date: May 7, 2014
Date: May 6, 2015
Estimated time to complete
these activities: 120 minutes. These activities have been approved for a
maximum of 2.0 AMA PRA
Category 1 Credit™ and 2.0 contact hour for nurses. There are
no fees or prerequisites.
by independent educational grants from
Serono and Genzyme, a Sanofi Company.
After participating in this
activity, the participant will demonstrate the ability to:
the importance of providing preconception counseling to all patients
of childbearing age in order to reduce reproductive risks.
the most recent evidence concerning the reproductive safety of
approved DMTs when counseling patients with MS who are considering
pregnancy or those who are pregnant.
and provide context for the available data (animal and human)
concerning the reproductive safety of newer and emerging DMTs.
the available evidence regarding DMTs and male reproductive health in
order to effectively communicate their potential risks to male
patients with MS.
the evidence on the safety of DMTs used during lactation, in order to
optimize outcomes for patients with MS who breastfeed their infants.
evidence-based treatment strategies to optimize the management of
The Johns Hopkins University
School of Medicine takes responsibility for the content, quality, and
scientific integrity of this CME activity.
Statement of Need
Multiple sclerosis typically
affects women of childbearing age and can influence fertility, pregnancy
and decisions regarding breastfeeding. Management of a pregnant patient
with MS or a patient contemplating pregnancy presents many unique issues
and can be quite challenging.
The intent of this Clinical
Dialogue, a video-based activity, is to review the most up-to-date evidence
on MS, specifically on fertility and pregnancy outcomes, management of MS
during pregnancy, the reproductive safety of DMTs, their use when
breastfeeding and issues related to postpartum management. We will also
address preconception issues, including pregnancy outcomes when it is the
male patient who has MS. The eCase Challenge, a text-based activity, will
allow the participant to apply the knowledge gained from this Clinical
Dialogue in a few real-world clinical scenarios.
It is important to emphasize
that the questions and answers discussed in this program must be
individualized to the specific circumstances of each patient and their
acceptance of risk.
Johns Hopkins Chair
and Course Director:
Jack N. Ratchford, MD
Assistant Professor of
Johns Hopkins University
School of Medicine
Jack N. Ratchford, MD
Assistant Professor of
Johns Hopkins University
School of Medicine
Patricia K. Coyle, MD
Professor and Vice Chair
Department of Neurology
Director, Multiple Sclerosis
Comprehensive Care Center
SUNY at Stony Brook
University Medical Center
Stony Brook, NY
Lynn Stazzone, RN,
MSN, NP, MSCN
Partners MS Center
Brigham and Women's Hospital
specifically, neurologists, internists, family practice physicians, nurse
practitioners, physician assistants, registered nurses and other providers
involved in the care of patients with multiple sclerosis.
Jointly presented by the
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The Johns Hopkins University
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Aggressor cells, which have the potential to cause autoimmunity, are targeted by treatment, causing conversion of these cells to protector cells. Gene expression changes gradually at each stage of treatment, as illustrated by the color changes in this series of heat maps. (Credit: University of Bristol/Dr. Bronwen Burton ---------------------------------------------
Jessica Berman -
September 04, 2014
Using allergy treatment as a model, researchers have figured out a way to switch off autoimmune diseases in which the body attacks its own tissues, and making the immune system protective against disease. The therapy could represent a revolution in the treatment of autoimmune ailments such as multiple sclerosis and lupus.
The immune system protects against illness by recognizing and attacking harmful microbial invaders, including bacteria, viruses and parasites. But in people with an autoimmune disease, such as multiple sclerosis, Type 1 diabetes, lupus or Grave’s disease, those protective immune system cells mistakenly attack the body’s own tissues.
Now, researchers at the University of Bristol in Britain have figured out a way to switch off that attack in a mouse model of multiple sclerosis. They exposed the animals to the antigens, or the proteins that are attacked in MS. That not only quieted the immune system, but turned it into a protective mechanism against disease.
The therapy is similar to the treatment for environmental allergies. Patients are injected with small amounts of the harmless pollen or dust antigens that make the body overreact, causing sneezing, rashes and itchy, watery eyes.
Eventually the immune system becomes desensitized to the irritant, and retrained not to produce an allergic reaction.
“We restore sort of a state of immune normality in these people," said researcher Bronwyn Burton, who works with the MS study. "So, hopefully they will still be able to respond to infections, they are able to fight off infections very readily, but they will not be able to mount these devastating autoimmune responses anymore."
Multiple sclerosis causes paralysis when the body attacks the protective outer coating of nerve cells, called myelin, thwarting motor impulses from the brain that control movement.
Researchers gave a gradually escalating dose of myelin antigens to the mice with MS-like disease, gradually switching off the misdirected immune attack.
The work is described in the journal Nature Communications.
Information provided by Cherie C. Binns RN BS MSCN
The relationship between smoking and a higher risk of MS has been well established. We have previously posted news articles describing this association, as well as evidence that smoking is associated with more severe MS symptoms.
Two new studies examining the relationship between MS and smoking have recently been published in the Journal of Clinical Neuroscience and the Journal of Neurology, led by Dr Cullen O’Gorman and Professor Simon Broadley from Griffith University in Queensland.
The first of these studies aimed to confirm the relationship between smoking and the risk of developing MS, in a sample of people from Queensland. This study was conducted on 560 people with MS and 480 controls, and the researchers found that in both current and ex-smokers, there was a small but significant increased risk of MS that was marginally higher in males.
The second study looked at the strength of this relationship across previously published studies. The team used statistical methods to combine the findings of 26 published studies into a ‘meta-analysis’, including data from 8,615 people with MS and 392,352 controls. Meta-analysis is considered one of the most robust types of analysis because of the large total number of people included. In this meta-analysis, the overall analysis provided support for a statistically significant increased risk of developing MS in both current and past smokers.
Then, the researchers identified that there are other factors which appear to have an important effect on the relationship between smoking and MS, such as where you live. In particular, they found that smoking was a stronger risk factor for MS in females who live closer to the equator, compared to females who live at higher latitudes. This latitude effect was not present in males.
Taking the two studies together, these findings suggest that environmental factors such as smoking and latitude may affect males and females differently. In regions at higher latitudes (further from the equator), smoking may have less effect on MS risk because these regions typically also have high rates of vitamin D deficiency, which has been strongly associated with MS risk. However, in areas of lower latitude such as Queensland, that are less affected by vitamin D deficiency, other risk factors such as smoking may have greater influence on the development of MS. Smoking is known to reduce vitamin D levels and this may contribute to the observed relationship.
These results provide greater insight into the relationship between smoking and MS, and help to piece together the complex interactions between genes and environment that underpin the development of MS.
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Now that all 5 eCase Challenges
focused on real-life MS cases have launched, we are providing all
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these programs. The University of Texas Southwestern Medical Center and
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These activities are
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assistants, registered nurses and other providers involved in the care of
patients with multiple sclerosis.
These activities have been
planned and implemented in accordance with the Essential Areas and
policies of the Accreditation Council for Continuing Medical Education
through the joint sponsorship of The University of Texas Southwestern
Medical Center and Medical Logix LLC. The University of Texas
Southwestern Medical Center is accredited by the ACCME to provide
continuing medical education for physicians.
Postgraduate Institute for
Medicine is accredited as a provider of continuing nursing education by
the American Nurses Credentialing Center's Commission on Accreditation.
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credit commensurate with the extent of their participation in the
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Keep CURRENT and up to date, with MS News and Information
- Data Further Support Industry-Leading Portfolio of MS Treatments and Innovative Pipeline Therapies -
- Innovative Programs Reinforce Commitment to Improving the Lives of People Living with MS -
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Biogen Idec (NASDAQ: BIIB) will present more than 90 company-sponsored platform and poster presentations on data supporting its marketed and investigational therapies for multiple sclerosis (MS), as well as the company’s programs to address unmet needs in patient management, at the sixth Triennial Joint Meeting of ACTRIMS and ECTRIMS in Boston, September 10 – 13, 2014. The breadth and volume of data exemplify Biogen Idec’s industry-leading expertise in research and development, comprehensive product portfolio, and enduring commitment to the MS community. ACTRIMS-ECTRIMS is the joint meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS).
“We are dedicated to advancing MS care through innovative clinical research on promising CNS targets with the potential for treating this disease and through novel initiatives that address critical disease management issues,” said Douglas E. Williams, Ph.D., executive vice president, Research and Development at Biogen Idec. “This includes our collaboration with the MS community to better understand the patient experience to help patients and physicians better work together to manage the disease.”
Biogen Idec data to be presented at ACTRIMS-ECTRIMS include results from studies of its currently approved products, TECFIDERA® [delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF)], TYSABRI® (natalizumab), FAMPYRA® (prolonged-release fampridine tablets) and PLEGRIDY™ (peginterferon beta-1a), as well as findings from the clinical programs of its MS pipeline candidates, ZINBRYTA™ [daclizumab high-yield process (DAC HYP)] and Anti-LINGO-1 (BIIB033).
Biogen Idec will also present information on several of the company’s initiatives that seek novel solutions to improve MS patient management, reinforcing the company’s commitment to comprehensively meet the needs of people with MS. These include highlights from the Value-Based Medicine (VBM) group, focused on developing and deploying new technology to help enhance individualized treatment decisions and a consensus opinion study of U.S. neurologists to assess practice patterns in the management of MS, and to inform U.S. consensus guidelines for treatment initiation. Additionally, highlights from an international survey of patients and neurologists designed to understand the current “State of MS,” including the quality of communication between MS patients and their physicians, will be presented.
Biogen Idec will also host a journalist and advocacy group briefing about the “State of MS” survey findings on Wednesday, September 10 at 11:30 a.m. – 1 p.m. EST. The discussion will focus on the relationship and communication between neurologists and people living with MS.
Highlights of Biogen Idec’s ACTRIMS-ECTRIMS Data
EMERGING APPROACHES TO MS MANAGEMENT
Consensus Opinion of U.S. Neurologists on Practice Patterns in Radiologically and Clinically Isolated Syndrome and Relapsing-Remitting MS – Poster #295 – Thursday, September 11, 2014 – 3:30-5:00 PM
The State of MS: Current Insight Into Patient-Neurologist Relationships, Barriers to Communication, and Treatment Satisfaction– Poster P824 – Friday, September 12, 2014 – 2:45-4:15 PM
Value Based Medicine: Enabling Evidence-Based and Individualized Treatment Decisions for Patients With Multiple Sclerosis – Poster P825 – Friday, September 12, 2014 – 2:45-4:15 PM
Five-Year Follow-up of Delayed-Release Dimethyl Fumarate in RRMS: Integrated Clinical Efficacy Data from the DEFINE, CONFIRM, and ENDORSE Studies – Poster P110 – Thursday, September 11, 2014 – 3:30-5:30 PM
Long-term Follow-up of the Effect of Delayed-Release Dimethyl Fumarate on No Evident Disease Activity in Patients with Multiple Sclerosis – Platform FC3.5 – Friday, September 12, 2014 – 9:03 AM
Correlations Between Patient-reported Ambulatory Function (MSWS-12) and Objective Disability Measurements in SPMS: Analysis of ASCEND Baseline Data – Poster P777 – Friday, September 12 – 2:45 – 4:15 PM
Effect of Peginterferon Beta-1a on MRI Measures and Freedom From Measured Disease Activity: 2-year Results From the Phase 3 ADVANCE Study – Poster P067 – Thursday, September 11, 2014 – 3:30-5:00 PM
Clinical Efficacy of Peginterferon Beta-1a in Relapsing-Remitting Multiple Sclerosis: 2-year Data From the Phase 3 ADVANCE Study – Platform FC2.5– Friday, September 12, 2014 – 9:03 AM
Psychometric Testing of the Early Mobility Impairment Questionnaire for Multiple Sclerosis – Poster P784 – Friday, September 12, 2014 – 2:45-4:15 PM
Walking Ability and Balance in Patients with Multiple Sclerosis Treated with Prolonged-Release Fampridine: Randomized, Double-Blind MOBILE Study – Poster P922 – Friday, September 12, 2014 – 2:45-4:15 PM
Safety and Tolerability of Daclizumab HYP Treatment in Relapsing-Remitting Multiple Sclerosis: Results of the DECIDE Study – Poster P094 – Thursday, September 11, 2014 – 3:30-5:30 PM
Primary Results of DECIDE: A Randomized, Double-Blind, Double-Dummy, Active-Controlled Trial of Daclizumab HYP vs. Interferon Β-1a in RRMS Patients – Platform FC1.1 – Friday, September 12, 2014 – 8:15 AM
A Phase II Study of the Anti-LINGO-1 Monoclonal Antibody, BIIB033, in Subjects With Acute Optic Neuritis: Baseline Data – Poster P731 – Friday, September 12, 2014 – 2:45-4:15 PM
Full session details and data presentation listings for the 2014 Joint ACTRIMS-ECTRIMS Meeting can be found at the meeting website, http://www.msboston2014.org/.
Scientists believe they are close to developing a drug which could 'switch off' autoimmune diseases like Multiple Sclerosis by training the body to stop attacking itself
Scientists believe that regular injections could retrain the immune system and 'switch off' autoimmune diseases Photo: Simon Belcher/ Alamy
By Sarah Knapton, Science Correspondent - Sept 3, 2014
Scientists believe they have discovered a way to ‘switch off’ autoimmune diseases like multiple sclerosis or Type 1 diabetes by retraining the immune system.
Autoimmune diseases are so debilitating because they trick the body into attacking itself.
But a team at Bristol University has shown that the immune system can be taught to stop treating harmless everyday proteins as if they were dangerous invaders.
In Multiple Sclerosis (MS) the immune system attacks the myelin sheaths which protect nerve fibres.
The nerves carry messages to and from the brain and if they are disrupted it leads to a host or problems such as loss of mobility, vision impairment and fatigue.
However by synthesising proteins from the sheaths in a lab, and then injecting them into the blood stream at increasing doses, the body begins to learn that they are safe.
This type of therapy has already been used for allergies in a treatment known as ‘allgergic desensitisation’ but it’s only recently that scientists have thought that it could be useful elsewhere.
Researchers at the University of Bristol, said the ‘important breakthrough’ could improve the lives of millions of people who are suffering from a range of diseases.
First author Dr Bronwen Burton said: “The immune system works by recognising antigens which could cause infection.
“In allergies the immune system mounts a response to something like pollen or nuts because it wrongly believes they will harm the body.
“But in autoimmune diseases the immune systems sees little protein fragments in your own tissue as foreign invaders and starts attacking them.
“What we have found is that by synthesising those proteins in a soluble form we can desensitise the immune system by giving an escalating dose.”
The team hope that the breakthrough could lead to the development of immunotherapies for individual conditions, based on the protein or antigen that the body is responding too.
Results from two phase I human safety trials of an exploratory treatment aimed at repairing myelin damaged by multiple sclerosis have now been published. One to two treatments with Biogen Idec’s BIIB033 (anti-LINGO monoclonal antibody) were given by injection under the skin or into the vein of healthy volunteers and people with relapsing-remitting or secondary-progressive MS. No serious adverse safety events were reported, and although these studies were not designed to evaluate effectiveness, the results were considered positive and have led to a phase II trial, now underway in relapsing MS. The results were published on August 27, 2014 in the online journal Neurology® Neuroimmunology & Neuroinflammation.
“It’s encouraging to see an entirely new treatment strategy aimed at repairing MS myelin damage moving forward in clinical trials,” noted Dr. Timothy Coetzee, Chief Advocacy, Services and Research Officer at the National MS Society. “Repairing myelin may be the best way to protect the nervous system from MS damage, and it holds potential for restoring function that has been lost in people living with this disease,” he added.
Background: In MS, immune attacks lead to the loss of myelin that coats and protects nerve fibers in the brain and spinal cord. Repairing the nervous system was just a dream a few years ago. Today it holds significant promise as a strategy to restore the function that MS has taken from people; and reducing or stopping MS progression. This remarkable progress is due in large part to the National MS Society’s comprehensive efforts and multi-million dollar research investments. Today the Society is supporting 87 research projects in nervous system repair, with multi-year commitments totaling over $35 million.
The first human trials of anti-LINGO leverage research aimed at stimulating the body's natural healing abilities. LINGO is a protein seen in neurons and myelin-producing cells (oligodendrocytes), and blockading this protein with a monoclonal antibody called anti-LINGO has been shown to promote remyelination in animal models.
Details: In these first tests of anti-LINGO in humans, 72 healthy people and 47 people with relapsing-remitting MS or secondary-progressive MS were given anti-LINGO or inactive placebo by injection under the skin or into the vein. The participants with MS were given two treatments, two weeks apart.
All participants were monitored extensively for any signs of adverse reactions. There were no serious adverse safety events noted. The most common side effects included headache, upper respiratory tract infection, stuffy nose, GI symptoms and urinary tract infection, and these were experienced by participants who were on placebo as well as those who received doses of anti-LINGO.
Generally phase I studies are not designed to detect benefit, but largely to evaluate the safety and tolerability of exploratory therapies, to refine appropriate dosing, and to determine whether they reach their targets – in this case, the central nervous system. That is true of these trials, and there was no evidence from MRI or other tests that showed clear evidence that existing brain lesions healed from this short exposure to anti-LINGO. However, the safety, dosing and pharmacology results were considered positive and have led to the design and launch of a phase II trial by Biogen Idec, now underway in relapsing MS.
Read more about research into nervous system repair in MS.
About Multiple Sclerosis
Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.