Author Interviews, Multiple Sclerosis, Neurology, NYU/NYMC / 21.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23669" align="alignleft" width="159"]Dr-Leigh-Elkins-Charvet.jpg Dr. Leigh Elkins Charvet[/caption] 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).
Author Interviews, Multiple Sclerosis, PNAS / 12.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23383" align="alignleft" width="141"]Dr-Christian-Gruber.jpg Dr. Christian Gruber[/caption] 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).
Author Interviews, Microbiome, Multiple Sclerosis / 05.04.2016

MedicalResearch.com Interview with: [caption id="attachment_23164" align="alignleft" width="85"]Professor JF Cryan PhD Department of Anatomy and Neuroscience APC Microbiome Institute University College Cork Cork, Ireland Prof. John Cryan[/caption] 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.
Author Interviews, Diabetes, JAMA, Multiple Sclerosis / 10.03.2016

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.
Author Interviews, BMJ, Coffee, Karolinski Institute, Multiple Sclerosis / 04.03.2016

MedicalResearch.com Interview with: [caption id="attachment_22362" align="alignleft" width="200"]Anna Hedström PhD student Anna Hedström PhD student[/caption] Anna Hedström PhD student Karolinski Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies on the influence of coffee consumption on multiple sclerosis (MS) risk have yielded inconclusive results, perhaps largely due to statistical power problems since these studies comprised few cases. Caffeine consumption has a protective effect on neuroinflammation and demyelination in animal models of MS. We therefore aimed to investigate whether coffee consumption is associated with MS risk, using two large population-based case-control studies (a Swedish study comprising 1620 cases and 2788 controls, and a United States study comprising 1159 cases and 1172 controls). The risk of multiple sclerosis was reduced by approximately 30% among those who reported a high coffee consumption, around six cups daily, compared to those who reported no coffee consumption. The risk of multiple sclerosis decreased with increasing coffee consumption. Potentially important influential factors were taken into consideration, such as smoking and adolescent obesity.
Author Interviews, Cleveland Clinic, Lancet, Multiple Sclerosis / 16.02.2016

MedicalResearch.com Interview with: [caption id="attachment_21655" align="alignleft" width="155"]Dr Jeffrey A Cohen MD Neurological Institute Cleveland Clinic, Cleveland OH 44195, USA Dr. Jeffrey Cohen[/caption] 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.
Author Interviews, Brigham & Women's - Harvard, Multiple Sclerosis, Neurological Disorders, Stem Cells / 26.01.2016

MedicalResearch.com Interview with: Zhigang He, PhD, BM Professor of Neurology  and Michela Fagiolini, PhD Assistant Professor of Neurology F.M. Kirby Neurobiology Center, Department of Neurology Children’s Hospital, Harvard Medical School Boston, MA 02115, USA

Medical Research: What is the background for this study? Drs. Fagiolini and He: Brain or spinal cord injury is still a major medical problem and there is no effective treatment of promoting functional recovery. A key issue is the nerve fibers, or axons, connecting different brain regions are damaged and cannot be repaired. For example, the axons in the optic nerve are the only channels transmitting visual signals from eye to brain. If damaged, our brain will not be able to receive visual signals and be blinded. Thus, a logical therapy should be to stimulate damaged axons to regrow to the targets and reconnect the eyes and brain. Studies in the past from us and others revealed several approaches of promoting the regrowth of injured axons, but it was unknown whether these regenerated axons could form functional connections and mediate functional recovery. Medical Research: What are the main findings? Drs. Fagiolini and He:  What we discovered in this study is that these regenerated axons could form functional connections, synapses, in the brain targets, but surprisingly fail to mediate behavioral visual function recovery. In mammals, many long projecting axons are insulated by lipid-enriched myelin sheets which could significantly speed up nerve conduction and facilitate the functional coordination of different brain regions during behavior. Interestingly, we found that different from intact optic nerves, these regenerated axons fail to be myelinated and thus possess poor conductance. When we treat these mice with compounds that can improve nerve conduction, we do observe partial yet significant functional recovery. Thus, there are at least two pieces of information from this study:
  • First, axon regrowth might not enough for functional recovery, nerve conduction could be another hurdle;
  • Second, the combination of these manipulations could serve a proof-of-principle example for achieving functional recovery.
ALS, Alzheimer's - Dementia, Author Interviews, JAMA, Multiple Sclerosis, Neurological Disorders, Stem Cells / 12.01.2016

[caption id="attachment_20586" align="alignleft" width="200"]Prof. Dimitrios Karussis M.D., Ph.D. Professor of Neurology Head, Multiple Sclerosis Center Hadassah BrainLabs Prof. Dimitrios Karussis[/caption] MedicalResearch.com Interview with: Prof. Dimitrios Karussis M.D., Ph.D. Professor of Neurology Head, Multiple Sclerosis Center Hadassah BrainLabs Medical Research: What is the background for this study? What are the main findings? Prof. Karussis: BrainStorm Cell Therapeutics is developing innovative, autologous stem cell therapies for highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD).  Our technology, NurOwn™ is a first-of-its-kind approach that induces autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) to secrete Neurotrophic Growth Factors (NTFs).  These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases. Data from the clinical trials described in the recent issue of the Journal of American Medicine – Neurology (JAMA Neurology), suggest that NurOwn can help patients with ALS.  The two trials featured in the article, a phase 1/2 and a phase 2a, studied the transplantation NurOwn cells in ALS patients.  These trials confirmed the excellent safety profile of NurOwn and suggest a clinically meaningful effect. The investigators used two well established clinical endpoints that measure disease activity in ALS, the Revised ALS Functional Rating Scale and Forced Vital Capacity, and were able demonstrate a slowing of disease activity in the period following treatment.
Author Interviews, Multiple Sclerosis / 07.12.2015

[caption id="attachment_19879" align="alignleft" width="133"]Dr. Vittorio Gallo PhD Center for Neuroscience Research Children’s Research Institute Children’s National Medical Center Washington, DC 20010 Dr. Vittorio Gallo[/caption] 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.
Author Interviews, Lancet, Multiple Sclerosis, Pharmacology, UCLA / 07.12.2015

[caption id="attachment_19869" align="alignleft" width="150"]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[/caption] 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.
Author Interviews, Cleveland Clinic, JAMA, Multiple Sclerosis / 13.10.2015

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.
Author Interviews, Melatonin, Multiple Sclerosis / 12.09.2015

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.
Author Interviews, JAMA, Multiple Sclerosis, OBGYNE / 01.09.2015

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.
Author Interviews, Multiple Sclerosis, Salt-Sodium / 19.08.2015

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.
Author Interviews, Depression, Lancet, Multiple Sclerosis / 04.02.2015

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.
Author Interviews, Infections, Multiple Sclerosis / 20.01.2015

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.
Author Interviews, JAMA, Multiple Sclerosis / 31.12.2014

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.
Cleveland Clinic, Multiple Sclerosis / 16.09.2014

MedicalResearch.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.
Author Interviews, Multiple Sclerosis, Sleep Disorders, UC Davis / 14.09.2014

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).
Author Interviews, JAMA, Multiple Sclerosis / 05.09.2014

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.
Author Interviews, Multiple Sclerosis, Neurology, Salt-Sodium / 28.08.2014

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).
Author Interviews, BMJ, Multiple Sclerosis / 14.07.2014

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.
Author Interviews, Multiple Sclerosis, Neurology / 03.04.2014

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.
Author Interviews, Cannabis, Lancet, Multiple Sclerosis, Neurological Disorders / 24.07.2013

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.