Multiple Sclerosis: Rituximab Had Better Short and Medium Term Outcomes

MedicalResearch.com Interview with:
Fredrik Piehl MD PhD, prof. of Neurology

Neuroimmunology Unit. Dept Clinical Neuroscience
Neurology Dept.
Karolinska University Hospital (Solna)
Stockholm

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years we have seen a drastic increase in treatment options for relapsing-remitting multiple sclerosis (RRMS). However, it is difficult to deduce long term performance of different drugs based only on data from randomized controlled trials, since such trials are performed in selected patients without major co-morbidities and perhaps also enriched for those with a milder disease course. In addition, most trials only last for two years and lack relevant comparators. This lack of knowledge makes it difficult to predict if a drug will work or not for a given patient, in turn leading to frequent treatment switches but also different treatment practices across countries, regions or even between centers. This is also the case in Sweden, but with the additional aspect that some regions have opted to treat most newly diagnosed RRMS patients with rituximab (Rituxan/Mabthera), a drug not formally approved for RRMS, but with extensive safety data from other indications.

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Multiple Sclerosis: Functional Changes After Inflammation May Partly Explain Clinico-Radiological Paradox

MedicalResearch.com Interview with:
Netta Levin MD PhD
fMRI lab
Neurology Department
Hadassah Hebrew University Medical Center
Jerusalem 

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, manifesting with episodes of local inflammatory processes, called relapses. The most useful surrogate laboratory test for MS is magnetic resonance imaging (MRI), in which dissemination of demyelinating lesions in space and time are the hallmark of the disease. However, there is a discrepancy between the lesion load – the number, size, and location of the lesions – and the clinical state of the patients, reflected in their disability. This discrepancy is known as the “clinico-radiological paradox” and suggests that something other than the well-known mechanisms of demyelination, remyelination, and axonal loss may tip the scale of recovery from an acute episode. Global effects of the local damage and compensatory mechanisms were suggested as an explanation to this paradox.

In this study, we compared the visual system of patients with clinically isolated syndrome optic neuritis (ON) to patients with clinically isolated episodes in other functional systems, exploring changes, both anatomical and functional, caused to the system following the demyelinating episode. Optic neuritis was deemed a good in vivo model for studying the pathophysiology of tissue damage and repair in MS due to its characteristic clinical manifestation and to the visual pathways’ amenability to investigation using various techniques. To assess anatomical wiring ,i.e the white matter fibers themselves , we used diffusion tensor imaging (DTI). To assess functional networking as reflected by signal synchronization between distinct brain regions, we used resting state fMRI.

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Intestinal Microbiome Alterations May Trigger Immune Reactions Inducing Multiple Sclerosis

MedicalResearch.com Interview with:

Kouichi Ito, PhD Associate Professor Department of Neurology Robert Wood Johnson Medical School Rutgers

Dr. Kouichi Ito

Kouichi Ito, PhD
Associate Professor
Department of Neurology
Robert Wood Johnson Medical School
Rutgers

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), and breakdown of immune tolerance to CNS proteins has been suggested to initiate CNS autoimmunity. Although the mechanism underlying the breakdown of immune tolerance to CNS proteins is still unknown, gut microbiota has been suggested to be involved in disease initiation and progression.

To investigate the etiology of Multiple Sclerosis, we have created humanized transgenic mice expressing MHC class II and T cell receptor genes isolated from an Multiple Sclerosis patient and showed that gut dysbiosis, alteration in intestinal microbial composition, can induce gut leakiness and subsequently trigger the development of neurological deficits through activation of complement C3 and reduction of CBLB and Foxp3 genes.

This study suggests that gut dysbiosis is one of the possible etiological factors for Multiple Sclerosis.

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IQuity Developing RNA-Based Disease Activity Test for Multiple Sclerosis

MedicalResearch.com Interview with:

Dr. Chase Spurlock, Ph.D. Executive Officer at IQuity, Inc Nashville, Tennessee

Dr. Chase Spurlock

Dr. Chase Spurlock, Ph.D.
Executive Officer at IQuity, Inc
Nashville, Tennessee

IQuity is working to further develop RNA technologies that can be used to diagnose and treat Multiple Sclerosis. IQuity hopes to develop a ‘disease activity test’, which would help physicians determine when a patient is likely to relapse so that treatments can be timed for best effect.

 

MedicalResearch.com: What is the background for IQuity? What are its goals and mission?

Response: IQuity, Inc. is a biotechnology company that focuses on the research and development of innovative specialty diagnostic technology, specifically for autoimmune diseases. Our research has shown that autoimmune patients have distinct RNA expression patterns in their blood, and we have figured out how to leverage machine learning methods to analyze these RNA expression patterns and test for the presence of diseases like multiple sclerosis, IBS/IBD (Crohn’s and ulcerative colitis) and fibromyalgia. We collected patient samples from around the globe to match their RNA profiles against healthy and sick patient profiles we identified through our previous research. These tests led to the development of IQIsolate, our technology that informs the suite of tests which, when used even at the earliest onset of symptoms, can give providers information to rule in or rule out a suspected autoimmune disease with more than 90% accuracy.

Our mission is to relentlessly pursue innovation in specialized diagnostic and analytic technology, identifying complicated autoimmune and autoimmune-related diseases at the earliest signs of symptoms. We strive to enable providers to diagnose early and treat sooner in the disease progression to improve long-term outcomes, lower the overall cost of lifelong autoimmune diseases and minimize the uncertainty and fear patients experience during prolonged diagnosis periods.

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Multiple Sclerosis Patients Show Cognitive Benefit From Remotely Supervised Transcranial Direct Current Stimulation

MedicalResearch.com Interview with:

Leigh E. Charvet, PhD Associate Professor, Department of Neurology Department of Neurology New York University Langone Medical Center New York, NY

Dr. Charvet

Leigh E. Charvet, PhD
Associate Professor, Department of Neurology
Department of Neurology
New York University Langone Medical Center
New York, NY

MedicalResearch.com: What is the background for transcranial direct current stimulation? What are the main findings of this study in multiple sclerosis patients?

Response: The application of tDCS is a relatively recent therapeutic development that utilizes low amplitude direct currents to induce changes in cortical excitability. When paired with a rehabilitation activity, it may improve learning rates and outcomes.

Multiple repeated sessions are needed for both tDCS and cognitive training sessions to see a benefit. Because it is not feasible to have participants come to clinic daily for treatments, we developed a method to deliver tDCS paired with cognitive training (using computer-based training games) to patients at home. Our protocol uses a telemedicine platform with videoconferencing to assist study participants with all the procedures and to ensure safety and consistency across treatment sessions.

When testing our methods, we enrolled 25 participants with multiple sclerosis (MS) completed 10 sessions of tDCS (2.0 mA x 20 minutes, dorsolateral prefrontal cortex, left anodal) using the remotely-supervised telerehabilitation protocol. This group was compared to n=20 MS participants who completed 10 sessions of cognitive training only (also through remote supervision).

We administered cognitive testing measures at baseline and study end. We found that both the tDCS and cognitive training only group had similar and slight improvements on composites of standard neuropsychological measures and basic attention. However, the tDCS group had a significantly greater gain on computer-based measures of complex attention and on a measure of intra-individual variability in response times.

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Long Term Fampridine (AMPYRA) Improves Gait Function in Multiple Sclerosis

MedicalResearch.com Interview with:

Linard Filli, PhD Gait Research Lab Department of Neurology University Hospital Zurich Zürich

Dr. Linard Filli

Linard Filli, PhD
Gait Research Lab
Department of Neurology
University Hospital Zurich
Zürich

MedicalResearch.com: What is the background for this study?

Response: Gait dysfunction is common in patients with multiple sclerosis (MS) and is perceived as the most restricting of symptoms. Fampridine (4-aminopyridine, dalfampridine), a blocker of voltage-gated potassium channels, is currently the only approved medication for the symptomatic treatment of walking disorders in patients in both the early and late phases of  multiple sclerosis.

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Multiple Treatment Options Now Available for Multiple Sclerosis

MedicalResearch.com Interview with:

Tomas Kalincik, MD, PhD, PGCertBiostat Neurologist and Senior Research Fellow Melbourne Brain Centre | Department of Medicine | University of Melbourne Department of Neurology | Royal Melbourne Hospital Melbourne | Victoria | Australia

Dr. Tomas Kalincik

Tomas Kalincik, MD, PhD, PGCertBiostat
Neurologist and Senior Research Fellow
Melbourne Brain Centre | Department of Medicine | University of Melbourne
Department of Neurology | Royal Melbourne Hospital
Melbourne | Victoria | Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multiple sclerosis is a disease predominantly of young adults, with the peak of incidence in the 3rd and 4th decades. It is the most common cause of neurological disability in young adults. Only in Australia, 23,000 people are living with MS, with MS representing an annual cost of almost 1 billion $AU to the Australian society. It is a disease that presents with broad range of neurological symptoms and signs, which are typically temporary (these are called relapses) that with time can lead to permanent neurological disability. While there is currently no cure for MS, with appropriate therapy, its symptoms can be controlled and the disability progression slowed down.

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CSF Biomarker May Signal Progression of Clinically Isolated Syndrome to MS

MedicalResearch.com Interview with:

Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, PB 2040 Rotterdam

Prof Rogier Q Hintzen

Prof Rogier Q Hintzen
Neurologist/immunologist
Head MS Centre ErasMS
Dept of Neurology
Erasmus MC, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Years ago, we identified soluble (s) CD27 as a biomarker for T cell activation in body fluids, as part of my PhD study. (J Immunol. 1991 Jul 1;147(1):29-35.)
As we presume the neuropathology seen in MS is guided by T cells we were interested to be able to quantify the activity of such cells in a given patient.
Cerebrospinal fluid (CSF) is as close as we can get to the site of the disease process in MS, therefore we focus on biomarkers in this compartment.
We found clearly elevated levels of sCD27 in CSF of Multiple Sclerosis patients versus non-inflammatory controls.

In this study we investigated whether at the moment of first attack of suspected Multiple Sclerosis, quantification of CSF sCD27 can predict further progression in to a diagnosis of MS and whether sCD27 levels are correlated with later attack frequency. Indeed, we found that high sCD27 measured at this early stage predicts a more rapid diagnosis of Multiple Sclerosis and a more aggressive disease course.

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Mutliple Sclerosis: Ocrelizumab Lowers Rate of Disease Progression and Disability

MedicalResearch.com Interview with:

Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030

Dr. Jerry Wolinsky,

Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.

However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.

The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.

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Multiple Sclerosis: Brain Atrophy Linked to Leaked Hemoglobin

MedicalResearch.com Interview with:

Charles Bangham PhD ScD Division of Infectious Diseases, Department of Medicine Imperial College London London, UK

Dr. Charles Bangham

Charles Bangham PhD ScD
Division of Infectious Diseases, Department of Medicine
Imperial College London
London, UK

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) is a neurological disease of the brain and spinal cord, often beginning in the 20s and 30s which can cause both attacks (relapses) and disability over time. Most people with the condition have intermittent episodes of illness at first, but about two-thirds go on to develop a progressive form, known as secondary progressive MS. In this form, there is a gradual loss of nerve cells in the brain, resulting in shrinkage of the brain and progressive disability.

Neither the initiating cause of  Multiple sclerosis nor the reasons for this brain shrinkage are known, and existing treatments for the early phase of the condition are unsatisfactory.

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Multiple Sclerosis: Interim Report on the Safety and Efficacy of Long-Term Daclizumab Treatment for Up to Five Years

MedicalResearch.com Interview with
Ralph Kern, M.D.
Senior vice president, Worldwide Medical
Biogen

MedicalResearch.com: What is the background for this study?

Response: Previously reported clinical trials of daclizumab demonstrated significant efficacy across clinical and MRI measures, compared to placebo and interferon beta-1a 30 mcg intramuscular (IM) injection, and established the therapy’s safety profile for up to two to three years. These trials were the basis for approval by health authorities in the United States, European Union and Australia. Daclizumab is a once-monthly, self-administered, subcutaneous therapy for relapsing forms of MS (RMS).

At ECTRIMS we presented the first interim results from EXTEND, a long-term extension study. EXTEND is an ongoing multicenter, open-label study to evaluate the safety and efficacy of daclizumab treatment in more than 1,500 patients with RMS.

This interim ECTRIMS analysis includes up to five years of data from patients who were previously enrolled in DECIDE. DECIDE was a Phase 3 study evaluating the effects of daclizumab relative to interferon beta-1a IM. In the new analysis, patients who were treated with interferon beta-1a IM for two to three years in DECIDE switched to daclizumab when they enrolled in EXTEND, and were compared to daclizumab patients treated continuously in both DECIDE and EXTEND.

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Patient Retention With DMTs vs Gilenya in Adults With Relapsing-Remitting Multiple Sclerosis

MedicalResearch.com Interview with:
Marcia Kayath, MD
Vice President and Head
US Clinical Development and Medical Affairs US General Medicines
Novartis Pharmaceuticals Corporation

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Injectable disease-modifying therapies (DMTs) are typically used first-line in patients with multiple sclerosis (MS), but discontinuation of injectable DMTs is common, especially within the first 12 months of treatment1,2. PREFERMS is the largest, prospective, randomized, active-controlled, open-label study to evaluate patient retention in patients with relapsing-remitting multiple sclerosis (RRMS).

In the 12-month, Phase IV study, a total of 875 patients were randomized (1:1) to Gilenya® (fingolimod) 0.5 mg or to a pre-selected injectable DMT (IFNβ-1a, IFNβ-1b or glatiramer acetate), and followed up quarterly for 12 months3. After a minimum of 3 months of treatment, a single on-study treatment switch was allowed, however, switches due to efficacy or safety were allowed (based on patient-doctor consultation) at any month following randomization3. The primary endpoint was to compare the patient retention on randomized treatment over 12 months3. This study was powered for the primary endpoint (retention rate)3. The study was not powered to detect the treatment difference in the secondary efficacy endpoints or treatment effects related to switching study medication3. Continue reading

Multiple Sclerosis Patients Have Altered Microbiome That May Benefit From Dietary Changes

MedicalResearch.com Interview with:

Ashutosh K Mangalam PhD Assistant Professor Department of Pathology University of Iowa Iowa City, IA

Mangalam~Ashu

Ashutosh K Mangalam PhD
Assistant Professor
Department of Pathology
University of Iowa
Iowa City, IA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Every human carries trillions of bacteria in their gut (gut microbiome) and recent advances in research indicate that these tiny passengers play an important role in our overall health maintenance. Having evolved over the time span of millions of years with the gut microbiome, they keep us healthy in multiple ways such as fermentation and absorption of undigested carbohydrates, synthesis of some vitamins, metabolism of bile acids etc.

However, new research suggests that gut microbiome, also regulating our body’s defense system. It is hypothesized that a diverse gut microbiome is good for our health and perturbations in this might predispose us to disease development. Therefore, we asked whether multiple sclerosis (MS) patients have a gut microbiome which is distinct from healthy individuals. We collected fecal samples from MS patients and healthy controls and performed microbiome analysis. I have recently moved to UI but the entire study was completed at Mayo Clinic Rochester. This study involved a big team comprised of neurologist, gastroenterologist, bioinformatician, system biologist and study coordinators. We found that  multiple sclerosis patients indeed have a gut microbiome which is different from what is observed in healthy people. We identified certain bacteria which are increased or decreased in the gut of patients with multiple sclerosis compared to healthy controls.

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Mitoxantrone for Severe MS Linked To Increased Risk of Colon Cancer and Leukemia

MedicalResearch.com Interview with:

PD Dr. Mathias Buttmann Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic University of Wuerzburg Wuerzburg, German

Dr. Mathias Buttmann

PD Dr. Mathias Buttmann
Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic
University of Wuerzburg
Wuerzburg, Germany 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated  multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer.

Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer.

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About 10% Rebound of Multiple Sclerosis When Immunomodulator Fingolimod Stopped

MedicalResearch.com Interview with:

Jennifer Graves, MD, PhD, MAS UCSF Adult and Pediatric MS Centers

Dr. Jennifer Graves

Jennifer Graves, MD, PhD, MAS
Adult and Pediatric Multiple Sclerosis Centers
UCSF

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Graves: Cessation of medications with effects on immune trafficking may be more likely to cause rebound inflammatory activity in autoimmune diseases such as multiple sclerosis.  We observed 5 strikingly severe relapses consistent with rebound events following cessation of fingolimod treatment and identified several similar cases in the literature.  At our center the rebound events occurred with an approximate 10% frequency.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Graves: Fingolimod cessation may be complicated by rebound phenomena in some patients, similar to what has been observed with natalizumab. Both of these medications have effects on immune cell trafficking, likely explaining the association with rebound events.  Careful consideration must be taken in stopping these medications.

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Olfactory Identification Predict Cognitive Impairment in Pediatric Onset Multiple Sclerosis

MedicalResearch.com Interview with:

Dr-Leigh-Elkins-Charvet.jpg

Dr. Leigh Elkins Charvet

Leigh Elkins Charvet, PhD
Director of MS Research
Multiple Sclerosis Comprehensive Care Center
Associate Professor of Neurology
NYU Langone Medical Center
New York, NY 10016

MedicalResearch.com: What is the background for this study?

Dr. Charvet One of the goals of our work is to identify cognitive impairment at the earliest point that it occurs in multiple sclerosis (MS), and ultimately to predict those who are at greatest risk.  Olfactory impairment is a feature of neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease and predicts cognitive decline.  Olfactory impairment has also been reported in adults with multiple sclerosis.  Our study, lead by Colleen Schwarz, measured olfactory identification and its link to cognitive performance in a subpopulation of those with earliest onset of MS—pediatric onset multiple sclerosis (POMS, referring to those with onset before the age of 18).

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New Class of Herbal Peptides May Ameliorate Multiple Sclerosis Symptoms

MedicalResearch.com Interview with:

Dr-Christian-Gruber.jpg

Dr. Christian Gruber

Dr. Christian W. Gruber PhD
Assistant Professor tenure-track and ARC Future Fellow
The University of Queensland,
School of Biomedical Sciences, Australia
Medical University of Vienna,
Center for Physiology and Pharmacology,
Vienna, Austria 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Gruber: We initially discovered that particular circular peptides (called cyclotides) isolated from an African traditional herbal medicine have promising immunosuppressive properties (Gründemann et al., 2012, J Nat Prod, 75(2):167-74).

Cyclotides are considered a pharmacological ‘treasure trove’ (Koehbach et al., 2013, PNAS, 110(52):21183-8). Hence we aimed at testing the efficacy of these peptides to treat and ameliorate multiple sclerosis, and found that the new plant-derived drug (‘T20K’), in an animal model, can block the progression of the disease. We demonstrated in an animal model that T20K stopped progression of the normal clinical symptoms of multiple sclerosis (Thell et al., PNAS, doi: 10.1073/pnas.1519960113).

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Gut Microbiome May Play Role in Myelination Disorders Including Multiple Sclerosis

MedicalResearch.com Interview with:

Professor JF Cryan PhD Department of Anatomy and Neuroscience APC Microbiome Institute University College Cork Cork, Ireland

Prof. John Cryan

Professor JF Cryan PhD
Department of Anatomy and Neuroscience
APC Microbiome Institute
University College Cork
Cork, Ireland

MedicalResearch.com: What is the background for this study? What are the main findings? 

Prof. Cryan: Over the past decade there has been an ever growing body of preclinical studies that highlight an essential role of the gut microbiota in many aspects of physiology including and perhps most surprtisingly the brain . Germ-free animals are one useful approach used to establish causality in gut microbiota-brain relationships. This model has been extremely useful in establishing that the microbiota is essential for appropriate stress responsibility, anxiety-like behaviours, neurogenesis, blood-brain barrier function and microglia activity. From these findings we can see that there is a clear cut role for the microbiota in CNS developmental processes.

Here we wanted to investigate using next generation sequencing, as we had done previously in the amygdala what impact life without microbes has on transcriptional regulation in the prefrontal cortex, a brain region essential in many aspects of emotional behaviour. What we uncovered from this was that there was a large number of dysregulated genes in germ-free animals that have a direct role in myelination. We found increased expression levels of genes that encode for structural proteins that are key in forming the myelin sheath. We followed up this finding with transmission electron microscopy to identify whether this marked increase in myelin related gene expression was functional at a structural level. What we found was germ-free myelinated axons in the prefrontal cortex were hypermyelinated (lower g-ratio), they had thicker myelin sheaths compared to conventionally raised mice. Additionally we also had germ-free colonized animals, animals that were born germ-free but have been colonized with a conventional microbiome early in life. These animals displayed no change in myelin related gene expression and appeared to be indistinguishable from the conventional animals. However, at the protein levels they appeared to have increased myelin protein like germ-free mice. This could be due to the fact that these mice were germ-free for at least 3 weeks of life and the hypermyelinated axons had already been established before colonization. Really this shows that we can still target the microbiota in later life that can have an impact of myelin gene regulation.
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Critical To Treat Comorbidities That Worsen Course of Multiple Sclerosis

MedicalResearch.com Interview with:
Jorge Correale MD

Department of Neurology, Institute for Neurological Research Dr Raúl Carrea
Buenos Aires, Argentina

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Correale: First it is now well known that in parallel to the specific treatment of Multiple Sclerosis, those comorbidities that worsen the course of the disease should be treated. For example, cardiovascular diseases. Moreover there are in vitro and in animal models evidence of an anti-inflammatory role of compounds investigated in this publication evidence.

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Vitamin D Deficiency in Pregnancy May Raise Risk of Multiple Sclerosis In Offspring

MedicalResearch.com Interview with:
Kassandra Munger, Sc.D.
Harvard T.H. Chan School of Public Health

MedicalResearch.com: What is the background for this study?

Dr. Munger: Previous work has shown that adequate vitamin D nutrition is associated with a lower risk of multiple sclerosis (MS).  Results from studies examining whether adequate vitamin D exposure during early-life are also associated with a lower risk of MS have been mixed.  One study reported that daughters of mothers with high dietary vitamin D intake during their pregnancy had a reduced risk of multiple sclerosis, while two studies measuring 25-hydroxy vitamin D either in a blood sample from the pregnant mother or from a sample taken from the neonate, were not associated with future multiple sclerosis risk in the child.

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Immune Modulator Ozanimod Shows Promise in Multiple Sclerosis

MedicalResearch.com Interview with:

Dr Jeffrey A Cohen MD Neurological Institute Cleveland Clinic, Cleveland OH 44195, USA

Dr. Jeffrey Cohen

Dr Jeffrey A Cohen MD
Mellen Center, Neurological Institute
Cleveland Clinic, Cleveland
OH 44195, USA

Medical Research: What is the background for this study? What are the main findings?

Dr. Cohen: Fingolimod, a non-selective sphingosine 1-phosphate receptor (S1PR) modulator, was the first oral medication approved to treat relapsing multiple sclerosis.  Though generally well tolerated, fingolimod’s first dose cardiac effects and other potential adverse effects complicate its use.  Ozanimod is a selective S1PR modulator with several other potentially advantageous pharmacologic properties.

The results of phase 2 RADIANCE trial were recently published.  In this trial, participants were randomized to placebo (n=88), ozanimod 0.5 mg (n=87), or ozanimod 1 mg (n=83) PO once daily for 24 weeks.  The mean cumulative number of gadolinium-enhancing lesions on monthly MRI scans at weeks 12-24, the primary endpoint, was reduced from 11.1 +/- 29.9 with placebo to 1.5 +/- 3.7 with ozanimod 0.5 mg and 1.5 +/- 3.4 with ozanimod 1 mg (both p<0.0001).  Other MRI endpoints supported the primary endpoint.  Ozanimod was well tolerated with good safety.  Importantly, the dose up-titration protocol effectively mitigated first dose cardiac effects.

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Cellular Target Opens New Pathway For Multiple Sclerosis Therapy

Dr. Vittorio Gallo PhD Center for Neuroscience Research Children’s Research Institute Children’s National Medical Center Washington, DC 20010

Dr. Vittorio Gallo

MedicalResearch.com Interview with:
Dr. Vittorio Gallo PhD

Center for Neuroscience Research
Children’s Research Institute
Children’s National Medical Center
Washington, DC 20010

Medical Research: What is the background for this study? What are the main findings?

Dr. Gallo: Astrocytes are cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, and help maintain homeostasis. In many neurodegenerative disorders – including multiple sclerosis  (MS) –astrocytes undergo a cellular and biochemical transformation called reactive gliosis. This process significantly impacts – both positively and negatively – neural regeneration. Reactive astrocytes (RAs) synthesize and release a peptide called Endothelin-1 (ET-1). Gallo and his team previously demonstrated that ET-1 is expressed at high levels by RAs in multiple sclerosis (MS) lesions and that – in animal models of MS – this peptide inhibits repair by delaying oligodendrocyte maturation and remyelination. 

The main finding of the study published in Cell Reports is the identification of the cellular and molecular pathway that mediates the inhibitory effects of ET-1 on oligodendrocyte regeneration and remyelinaton in demyelinated lesions. In particular – by using pharmacological and genetic approaches – the study demonstrates that the ET-1 acts selectively through the ET-receptor B (ENDRB) on astrocytes – and not oligodendrocytes – to indirectly inhibit remyelination.

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Estriol Reduced Multiple Sclerosis Relapses

Professor Rhonda Voskuhl, M.D. Jack H. Skirball Chair in MS Research Director of the UCLA MS Program David Geffen School of Medicine University of California, Los Angeles

Prof. Voskuhl

MedicalResearch.com Interview with:
Professor Rhonda Voskuhl, M.D.
Jack H. Skirball Chair in MS Research
Director of the UCLA MS Program
David Geffen School of Medicine
University of California, Los Angeles

Medical Research: What is the background for this study? What are the main findings?

Dr. Voskuhl: It had been known for decades that relapses were reduced during pregnancy in women with Multiple Sclerosis (MS), psoriasis and rheumatoid arthritis. We viewed this as a major clue to help find new disease modifying treatments. Focusing on MS, we investigated treatment with estriol, an estrogen that is made by the fetus/placenta during pregnancy. Preclinical studies and a pilot clinical trial at UCLA showed good results leading to the current Phase 2 clinical trial at 16 sites across the U.S. It showed that treatment with estriol pills compared to placebo pills, each in combination with standard of care (glatirmar acetate) injections, reduced relapses by one third to one half over and above standard of care treatment.

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Generic Multiple Sclerosis Drug Found Equivalent To Brand Medication

Dr. Jeffrey Cohen MD Director Mellen Center for Multiple Sclerosis Treatment and Research Director of the Experimental Therapeutics Program Cleveland Clinic Main CampusMedicalResearch.com Interview with:
Dr. Jeffrey Cohen MD
Director
Mellen Center for Multiple Sclerosis Treatment and Research
Director of the Experimental Therapeutics Program
Cleveland Clinic Main Campus

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Cohen: Medications are a major contributor to the high cost of Multiple Sclerosis (MS) care.  As medications go off patent, there is the opportunity to develop generic versions with lower cost.  This trial was conducted after extensive in vitro and animal studies supported the equivalence of a generic glatiramer acetate to the brand drug Copaxone. The trial showed that generic and brand glatiramer acetate have equivalent efficacy as measured by MRI and clinical endpoints, safety, and tolerability.

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Study Suggests Further Research of Melatonin To Decrease MS Relapses Warranted

MedicalResearch.com Interview with:
Dr.
Mauricio F. Farez
Center for Research on Neuroimmunological Diseases (CIEN)
Raúl Carrea Institute for Neurological Research (FLENI)
Buenos Aires, Argentina

Medical Research: What is the background for this study? What are the main findings?

Dr. Farez: We were intrigued by our initial observation that Multiple Sclerosis (MS) relapses have a clear seasonal occurrence with less relapses during fall and winter. We found that melatonin levels (a hormone secreted by the pineal gland in the absence of light) have an inverse correlation with Multiple Sclerosis relapses. Moreover, melatonin controls the generation of pathogenic Th17 cells, while it boosts the generation of regulatory Tr1 cells. By affecting the immune balance of those cells it may prevents the occurrence of relapse.

Medical Research: What should clinicians and patients take away from your report?

Dr. Farez: Melatonin and drugs alike targeting its pathways may be a future alternative in Multiple Sclerosis  treatment. Until a proper clinical trial is conducted, melatonin SHOULD NOT be used as Multiple Sclerosis therapy. I would like to emphasize this, because melatonin is a complex hormone with receptors present basically in every cell. We do not know yet the dosage and administration form needed to obtain similar effects as the one observed in our in vitro and animal studies.
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Breastfeeding May Reduce Multiple Sclerosis Relapses

PD Dr. Kerstin Hellwig Neurologische Abteilung Universitätsklinikum St. Josef Hospital BochumMedicalResearch.com Interview with:
PD Dr. Kerstin Hellwig
Neurologische Abteilung Universitätsklinikum
St. Josef Hospital
Bochum

Medical Research: What is the background for this study? What are the main findings?

Dr. Hellwig: The relapse risk is elevated in women with Multiple Sclerosis after delivery. We found that women with Multiple Sclerosis who breastfed exclusively had a significant lower relapse risk, than women who did not breastfed at all or breastfed some
but not exclusively. After the introduction of supplemental feedings,
the relase risk was similar between both groups.

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Could Increased Salt In Processed Food Contribute To Rise in MS Cases?

Dimitry N. Krementsov PhD Research Associate University of Vermont Burlington, VT 05405MedicalResearch.com Interview with:
Dimitry N. Krementsov PhD
Research Associate
University of Vermont
Burlington, VT 05405

Medical Research: What is the background for this study? What are the main findings?

Dr. Krementsov:  Multiple sclerosis (MS) is the most common disabling neurologic disorder affecting young adults. The disease is initiated by the individual’s own immune system attacking the central nervous system (brain and spinal cord).Multiple sclerosis is complex and is controlled by the interplay between sex/gender, genetics, and environmental factors. How this happens is not well understood, but an intriguing clue is that MS incidence over the last 50-100 years has been increasing in women and not men, suggesting that a recent environmental change is affecting MS preferentially in females.

There are several well-documented risk factors for Multiple Scleroisis, including Epstein-Barr virus infection, low sunlight exposure, low vitamin D, and smoking. Recent studies have suggested the existence of a new risk factor – high intake of dietary salt. In our study, we sought to understand how this environmental factor may interact with genetics and sex.

We used an animal model of MS, called experimental autoimmune encephalomyelitis (EAE), in laboratory mice. The advantage of this approach is the ability to precisely control both the genetics and the environment, something that cannot be done in epidemiological studies in humans. Just as in previous studies, we found that when mice were fed a high salt diet, their MS-like disease got worse.

Importantly, we found that this was dependent on genetics and sex; when we varied the genetic background of the mice, we saw three different outcomes:
1) an effect of salt in both males and females,
2) an effect only in females, and
3) no effect in either sex.

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Seizure Medication Reduced Optic Neuritis In Multiple Sclerosis

dr-raju-kapoor.jpgMedicalResearch.com Interview with:
Dr. Raj Kapoor
National Hospital for Neurology and Neurosurgery
University College London Hospitals NHS Foundation Trust

Medical Research: What is the background for this study?

Dr. Kapoor: Current treatments for Multiple Sclerosis do not prevent disability which accumulates from relapses, or which progresses between relapses. Experimental work suggests that the neurodegeneration which underlies disability could be prevented using agents which block voltage gated sodium channels. We have tested this possibility using treatment with the sodium channel blocker phenytoin in patients with acute optic neuritis. We tested whether phenytoin could prevent the degeneration seen in the retinal nerve fiber layer and macula after an attack of optic neuritis.

Medical Research: What are the main findings?

Dr. Kapoor: The main findings are that the group of patients treated with phenytoin had less degeneration in the retinal nerve fiber layer (rnfl) and in the macula (mv) in the eye affected by optic neuritis than the group treated with placebo. Phenytoin treatment reduced the degeneration by 30 % (rnfl) – 34% (mv).

Medical Research: What should clinicians and patients take away from your report?

Dr. Kapoor: This is a study designed to test the concept of neuroprotection, and it appears that the treatment was successful. Phenytoin did not lead to better vision after optic neuritis, but our trial was too small to determine whether phenytoin could achieve this. By providing proof of concept for the treatment target, however, and by demonstrating neuroprotection so robustly, we hope to open a door to even better treatments to prevent disability in Multiple Sclerosis.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Kapoor: The trial suggests that proof of neuroprotection using different treatment targets could be sought in similar trials in optic neuritis. Better treatment effects could be achieved by refining the trial design, for example by looking for drugs with more potent effects on the relevant sodium channels, by treating even earlier from the onset of optic neuritis, and by combining such neuroprotection with other treatments to promote remyelination and to suppress inflammation in Multiple Sclerosis.

Citation:

2015 AAN abstract :

Phenytoin is Neuroprotective in Acute Optic Neuritis: Results of a Phase 2 Randomized Controlled Trial

 

MedicalResearch.com Interview with: Dr. Raj Kapoor (2015). Seizure Medication Reduced Optic Neuritis In Multiple Sclerosis 

Computer Based Program Improved Depression in Multiple Sclerosis Patients

Dr Stefan M Gold Institute of Neuroimmunology and Multiple Sclerosis (INIMS) Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf Hamburg, GermanyMedicalResearch.com Interview with:
Dr Stefan M Gold

Institute of Neuroimmunology and Multiple Sclerosis (INIMS)
Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf
Hamburg, Germany

Medical Research: What is the background for this study? What are the main findings?

Dr. Gold: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (brain and the spinal cord). In addition to motor symptoms such as walking impairment, patients with Multiple sclerosis frequently suffer from psychological problems including difficulties with learning and memory as well as depressed mood. Depression is particularly common in this patient group with a 3-4 fold elevated risk for developing major depressive disorder compared to the general population. Depression in Multiple sclerosis is associated with decreased quality of life, absence from work, and numerous other psychosocial problems. Despite this major impact on patients’ lives, depression in Multiple sclerosis is often not adequately diagnosed and treated: Antidepressant medication in this patient group often has side effects and the neurological problems associated with MS such as difficulties with concentration and fatigue make it particularly difficult for MS patients to complete “classical” depression treatments such as psychotherapy. The goal of our study was to make psychological treatments available for the many patients with Multiple sclerosis suffering from depression, who often have difficulties to find adequate treatment.

For this study, published in The Lancet Psychiatry, we conducted a randomized controlled trial of a fully-automated, computer-based program that can be accessed directly from patients’ homes over the internet. The program called “deprexis” was developed by the Hamburg-based company GAIA and uses methods of “cognitive behavioral therapy” or “CBT”. Ninety Multiple sclerosis patients were enrolled in the trial and randomly assigned to a 3 months therapy using the deprexis program or a waitlist control group. At the end of the intervention, depression had significantly decreased in the treatment group but remained unchanged in patients who did not have access to the program. In addition, patients using the computer program also reported reduced fatigue and improved quality of life. Continue reading

Could H pylori Be Protective Against Multiple Sclerosis?

Allan G Kermode MBBS MD FRACP FRCP Clinical Professor of Neuroimmunology, Murdoch University Clinical Professor of Neurology, University of Western Australia Head, Department of Neurology and Clinical Neurophysiology SCGH Centre for Neuromuscular and Neurological Disorders Australian Neuromuscular Research Institute Sir Charles Gairdner Hospital Perth WA Australia Institute of Immunology and Infectious Diseases Murdoch University, Western AustraliaMedicalResearch.com Interview with:
Allan G Kermode MBBS MD FRACP FRCP

Clinical Professor of Neuroimmunology, Murdoch University
Clinical Professor of Neurology, University of Western Australia
Head, Department of Neurology and Clinical Neurophysiology SCGH
Centre for Neuromuscular and Neurological Disorders
Australian Neuromuscular Research Institute  Sir Charles Gairdner Hospital Perth WA Australia Institute of Immunology and Infectious Diseases
Murdoch University, Western Australia

MedicalResearch: You found that H. pylori sero-positivity was significantly lower in female patients with MS than in female healthy controls, but you didn’t find such a trend in men with Multiple Sclerosis… Briefly, what might explain this association between H. pylori and Multiple Sclerosis in women? (i.e the hygiene hypothesis I suppose?).

Prof. Kemode: There are a number of possible explanations, but we believe that the most likely is that helicobacter colonisation is a surrogate marker for the baseline levels of exposure to environmental pathogens and organisms during childhood. We have argued this point of view in our manuscript. It should be emphasised that perhaps not all exposure to infectious agents need necessarily be pathogenic, and the concept of the protobiome is an important one. Every healthy (and unhealthy) individual is host to very many organisms, with the gut having the widest diversity. Other explanations for the association might include that there is some specific antigenic interaction occurring promoting specific immune tolerance to CNS antigens, but I believe that this conclusion would be drawing a very long bow with our current stage of knowledge regarding Multiple Sclerosis.

MedicalResearch: Why does this relationship exist in women but not in men? (presumably, they are exposed to the same sanitation, hygiene etc.)

Prof. Kemode: This is arguably one of the most fascinating observations of our study. Historically the sex ratio in Multiple Sclerosis was equal, yet in the last 100 years the prevalence of Multiple Sclerosis has increased markedly and the majority of this increase has occurred in women such that in Australia the sex ratio F:M approximates 3:1. The fact that over the same period prevalence of helicobacter in Western countries has declined markedly is a tantalising observation. At this stage scientific knowledge has not explained the changing sex ratios in Multiple Sclerosis nor can we yet explain the strong helicobacter association in females but not males in our study, but our study provides useful navigation to direct further research.

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No Link Between HPV Vaccine and Multiple Sclerosis

Anders Hviid, M.Sc., Dr.Med.Sci. Senior Investigator, Statens Serum InstitutMedicalResearch.com Interview with:
Anders Hviid, M.Sc., Dr.Med.Sci.

Senior Investigator, Statens Serum Institut

Medical Research: What is the background for this study?

Response: After the widespread introduction of HPV vaccination of adolescent girls, a number of safety concerns have emerged. In this case, demyelinating diseases, including multiple sclerosis, occurring after HPV vaccination has been reported in social media, news media and medical journals.

Medical Research: What are the main findings?

Response: In a study of almost 4 million Danish and Swedish women, we found no support for an increased risk of multiple sclerosis or other demyelinating diseases following HPV vaccination. Continue reading

Multiple Sclerosis: Pilot Study of Immunosuppression Plus Transplantation

Dr. Richard Nash MD Colorado Blood Cancer InstituteMedicalResearch.com Interview with:
Dr. Richard Nash MD
Colorado Blood Cancer Institute

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Nash: Multiple sclerosis is an autoimmune disease of the central nervous system which causes significant disability and in some cases results in patients being wheel-chair bound or bed-ridden. It is a significant medical problem amongst young adults. We undertook this study because current Multiple sclerosis therapies were not adequate for effective long-term control of the disease in the majority of the patients. High-dose immunosuppressive therapy followed by autologous hematopoietic cell transplantation is an effective treatment for many hematological malignancies. It causes a profound immunosuppression. Based on this effect on the immunological system, we initiated a clinical trial of this treatment modified for autoimmune disorders. The study was supported by the Immune Tolerance Network and NIAID, NIH. In a phase 2 clinical trial of 25 patients all of whom were followed for at least 3 years, we demonstrated that 80% of patients had no evidence of disease activity. No other Multiple sclerosis treatments were given after the study treatment. Adverse events were similar to what we have observed for this treatment in patients with hematological malignancies. No significant acute neurological adverse events were observed. Continue reading

Multiple Sclerosis: Generic Copaxone Demonstrates Equivalent Safety and Efficacy

Jeffrey Cohen MD Department of Neurology Cleveland ClinicMedicalResearch.com: Interview with:
Jeffrey A. Cohen, MD
Hazel Prior Hostetler Endowed Chair
Professor, Cleveland Clinic Lerner College of Medicine
Director, Mellen Center for MS Treatment and Research
Neurological Institute
Cleveland Clinic Cleveland, OH  44195

Medical Research: What are the main findings of the study?

Dr. Cohen: The primary objective of the GATE trial was to compare the efficacy and safety of generic glatiramer acetate to the approved form (Copaxone) in relapsing-remitting multiple sclerosis.  The study demonstrated equivalent efficacy of generic glatiramer acetate and Copaxone measured by gadolinium enhancing brain MRI lesions at months 7, 8, and 9 and a number of additional measures of MRI lesion activity.  The study also showed comparable safety (measured by adverse events) and injection site tolerability.

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Multiple Sclerosis: Sleep Disorders Both Common and Underdiagnosed

Steven D. Brass, M.D., M.P.H., M.B.A. PI and Lead Author on the study Director of Neurology Sleep Clinical Program Co-Medical Director of Sleep Medicine Laboratory Associate Clinical Professor in the Department of Neurology UC Davis Health System 4860 Y Street — Suite 3700 Sacramento, CA 95817 MedicalResearch.com Interview with:
Steven D. Brass, M.D., M.P.H., M.B.A.
PI and Lead Author on the study
Director of Neurology Sleep Clinical Program
Co-Medical Director of Sleep Medicine Laboratory
Associate Clinical Professor in the Department of Neurology
UC Davis Health System 4860 Y Street — Suite 3700
Sacramento, CA 95817

Medical Research: What was the primary finding of your study?

Dr. Brass : Among the 11,400 surveys mailed out to all members of the Northern California Chapter of the National Multiple Sclerosis Society, 2,810 (24.6%) were returned. Of these, 2,375 (84.5%) met the inclusion criteria. Among the completed surveys, 898 (37.8%) screened positive for obstructive sleep apnea, 746 (31.6%) for moderate to severe insomnia, and 866 (36.8%) for restless legs syndrome.  In contrast, only 4%, 11%, and 12% of the cohort reported being diagnosed by a health care provider with obstructive sleep apnea, insomnia, and restless legs syndrome, respectively. Excessive daytime sleepiness was noted in 30% of respondents based on the Epworth Sleepiness Scale. More than 60% of the respondents reported an abnormal level of fatigue based on the Fatigue Severity Scale.  There was also an increased risk between complaints of Fatigue based on screening positive for the Fatigue Severity Scale  and screening positive for Obstructive Sleep Apnea  (1.850, with a 95% p-value < 0.001).

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Multiple Sclerosis: Slower Walking Speed Associated With Decreased Quality of Life

Jeffrey Cohen MD Department of Neurology Cleveland ClinicMedicalResearch.com Interview with:
Jeffrey Cohen MD
Department of Neurology
Cleveland Clinic

Medical Research: What are the main findings of the study?

Dr. Cohen: This study assessed the relationship between walking speed, as measured by the Timed 25-foot Walk test, and patient-reported quality of life, as measured by the Physical Component Summary score of the 36-Item Short Form Health Survey (SF-36), in a pooled dataset from the AFFIRM, SENTINEL, and IMPACT multiple sclerosis Phase 3 trials.  It showed that slowed walking speed is associated with decreased quality of life.  It also showed that 20-25% slowing of walking speed is a clinically meaningful change.
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Multiple Sclerosis: High Salt Intake Linked to More Relapses

MedicalResearch.com Interview with:
Dr. Mauricio Farez
Department of Neurology, Raúl Carrea Institute for Neurological Research
Buenos Aires, Argentina

Medical Research: What are the main findings of the study?

Dr. Farez: Our study shows that patients with Multiple Sclerosis (MS) with moderate to high sodium (salt) intake have also increased disease activity (more clinical relapses and more lesions on MRIs).

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Multiple Sclerosis: Clinical Features and MRI Changes of Decision-Making Difficulties

Dr Nils Muhlert Wellcome Trust ISSF Research Fellow School of Psychology Cardiff UniversityMedicalResearch.com Interview with:
Dr Nils Muhlert
Wellcome Trust ISSF Research Fellow
School of Psychology
Cardiff University

Medical Research: What are the main findings of the study?

Dr. Muhlert: Decision making impairments are known to occur in people with multiple sclerosis (MS), and are important, given they can contribute to employment status, treatment compliance and function in everyday life. Studies by Kleeberg, Simioni and others have demonstrated that decision-making impairments can occur early in the course of multiple sclerosis and get worse as the disease progresses. Questions however remain over whether these impairments are linked to more general cognitive difficulties, differences between multiple sclerosis subtypes, and their relationship with MRI changes.

We assessed decision-making and examined MRI changes in a relatively large sample of people with multiple sclerosis (N = 105) and healthy controls (N = 43). All participants performed the Cambridge Gambling Task, which independently measures risk-taking, impulsivity, deliberation and risk adjustment, and underwent an MRI scan including T1-weighted and diffusion MRI sequences.

We demonstrate that people with multiple sclerosis experience difficulties with risk adjustment (gauging risk and adapting accordingly) and in the speed of making decisions but not in impulsivity. These problems were seen in those classified as having cognitive impairment and those not (i.e. cognitively unimpaired). We found that decision-making impairments were twice as common in people with relapsing-remitting and primary progressive MS than healthy controls, and almost four times as common in people with secondary progressive multiple sclerosis. In addition, decision making impairments in multiple sclerosis were linked to MRI changes in regions previously linked to decision-making in other conditions, including fronto-striatal and hippocampal regions. These findings offer insight into the precise decision-making difficulties experienced by people with multiple sclerosis, the relative prevalences in different subtypes of the disease and the pathological processes that may underlie them.

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Multiple Sclerosis: Monoclonal Antibody Tysabri Reduces Brain Inflammation

Jeppe Romme Christensen  MD PhD From the Danish Multiple Sclerosis Center Copenhagen University Hospital Hvidovre, Denmark.MedicalResearch.com Interview with:
Jeppe Romme Christensen  MD PhD
From the Danish Multiple Sclerosis Center
Copenhagen University Hospital Hvidovre, Denmark.

MedicalResearch.com: What are the main findings of the study?

Dr. Christensen: This study demonstrates that progressive multiple sclerosis (MS) patients have reduced inflammation and tissue damage in the brain after treatment with natalizumab. These findings highlight that progressive MS is an inflammatory disease and furthermore that peripheral circulating immune cells contribute to brain inflammation and tissue damage in progressive MS.

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MS Progression: Cannabis Active Ingredient Ineffective

Professor John Zajicek Professor of Clinical Neuroscience, Centre for Clinical Trials & Health Research - Translational & Stratified Medicine (Peninsula Schools of Medicine and DentistrMedicalResearch.com Interview with:
Professor John Zajicek
Professor of Clinical Neuroscience, Centre for Clinical Trials & Health Research – Translational & Stratified Medicine (Peninsula Schools of Medicine and Dentistry)

MedicalResearch.com: What are the main findings of the study?

Prof. Zajicek: Our study investigated whether dronabinol (one of the major active ingredients of cannabis) may slow the progression of multiple sclerosis. We currently have no treatments that are effective in modifying the disease course in people with either primary or secondary MS. We did a clinical trial across the UK involving nearly 500 patients, who were randomly allocated to dronabinol or placebo, and followed them up for three years to look at progression on rates. Overall we failed to find an effect of dronabinol on disease progression,  either clinically (using a variety of clinical measures) or using magnetic resonance imaging (MRI). There was a suggestion of an effect in people with the least disability (who didn’t need a stick to help them walk), and there were no major problems with serious side effects.  However, over all the population that took part in the study also progressed less than we expected, which reduced our chances of finding an effect of treatment. The  study was not designed to investigate an effect on MS-related symptoms (such as pain and muscle stiffness), which have been investigated before.
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Incidence of multiple sclerosis in multiple racial and ethnic groups

MedicalResearch.com eInterview with Annette Langer-Gould, MD, PhD

From the Department of Research and Evaluation Kaiser Permanente,
Southern California, Pasadena; and Neurology Department
Kaiser Permanente, Southern California Los Angeles Medical Center, CA.

MedicalResearch.com: What are the main findings of the study?

Dr. Langer-Gould: The main findings of the study were that multiple sclerosis is more common in black women than in white women, which run contrary to the widely accepted belief that blacks are less susceptible to MS. In particular, we found that black patients had a 47 percent higher risk of MS than white patients, while Hispanic and Asian patients had a 50 percent and 80 percent lower risk compared to white patients, respectively. We also found that 70 percent of MS cases occurred in females, but this preponderance of females diagnosed was more pronounced among black patients than white patients. In addition, black women had a higher incidence of MS than white patients of both genders, while black men had a similar risk of being diagnosed with MS compared to white men. The lower risk among Hispanic and Asian patients was true for both sexes.
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New Multiple Sclerosis Gene Associations Discovered

An international team of scientists has identified 29 new genetic variants linked to multiple sclerosis, providing key insights into the biology of an important and very debilitating neurological disease.

Multiple sclerosis (MS), one of the most common neurological conditions among young adults, affects around 2.5 million individuals worldwide. It is a chronic disease that attacks the central nervous system (CNS), which includes the brain, spinal cord and optic nerves, and can cause severe symptoms such as paralysis or loss of vision.

Vanderbilt University Medical Center’s Center for Human Genetics Research (CHGR) played an important role in the research published today in the journal Nature, which represents the largest MS genetics study ever undertaken and effectively doubles the number of genes known to be associated with the disease.

“We now know just how complex multiple sclerosis is,” said Jonathan Haines, Ph.D., director of the CHGR and one of the principal researchers in this effort. “These new genes give us many new clues as to what is happening in MS and will guide our research efforts for years to come.”

Researchers studied the DNA from 9,772 individuals with multiple sclerosis and 17,376 unrelated healthy controls. They were able to confirm 23 previously known genetic associations and identified a further 29 new genetic variants (and an additional five that are strongly suspected) conferring susceptibility to the disease.

Many genes implicated in the study are relevant to the immune system, shedding light onto the immunological pathways that underlie the development of multiple sclerosis.

One-third of the genes identified in the study have previously been implicated in playing a role in other autoimmune diseases such as Crohn’s Disease and Type 1 diabetes, Haines said.

Previous studies have also suggested a link between vitamin D deficiency and an increased risk of multiple sclerosis; researchers in this study identified two genes involved in the metabolism of vitamin D, providing additional insight into a possible link between genetic and environmental risk factors.

The international team led by the Universities of Cambridge and Oxford, and funded by the Wellcome Trust, includes contributions from nearly 250 researchers as members of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium.