Author Interviews, Genetic Research, Infections, Neurological Disorders / 14.12.2022 Interview with: Dr. Eli Hatchwell, MA MB BChir (Cantab) DPhil (Oxon) BA (OU) Chief Scientific Officer Population Bio UK, Inc. Begbroke Science Park Begbroke Hill Begbroke, Oxfordshire United Kingdom What is the background for this study? Response: Progressive Multifocal Leukoencephalopathy (PML) is a devastating condition that is associated with a number of clinical situations, including treatment with a variety of drugs. Of these, the best known is natalizumab (Tysabri), which is a very successful drug in the treatment of MS (multiple sclerosis). Only a small proportion of patients treated with natalizumab develop PML and this has always been a mystery. The study was based on a hypothesis that some individuals have an underlying susceptibility to developing PML, based on the presence of variants in genes that are important in the immune system. The study identified several of these variants. (more…)
Author Interviews, Multiple Sclerosis / 19.01.2022 Interview with: Marcus Koch MD PhD Associate Professor of Neurology Multiple Sclerosis Program University of Calgary What is the background for this study? Response: Primary progressive multiple sclerosis (PPMS) is the least common, but also the least treatable form of multiple sclerosis. PPMS does not react well to commonly used MS treatments. We believe that this is at least in part because PPMS is driven by other disease mechanisms. One disease mechanism that we believe is important in PPMS is microglial activation. Microglial cells are a type of cell in the brain and spinal cord that normally have beneficial functions, such as clearing debris or assisting repair after injury. In PPMS however, microglial cells are chronically active, and we believe that this chronic microglial activation contributes to tissue damage. (more…)
Author Interviews, JAMA, Multiple Sclerosis, Neurology / 15.06.2020 Interview with: Cris S Constantinescu,  MD, PhD, FRCP Professor, Division of Clinical Neuroscience Research Group in Clinical Neurology University of Nottingham Queen's Medical Centre Nottingham UK What is the background for this study? Response: The study is in some way a test of the hygiene or old friends hypothesis, whereby eradication, through improved hygiene, of some parasites that have existed in the human gut for thousands of years and have suppressed inflammatory reactions, leads to an increase in inflammatory conditions. This has been used to explain the increased autoimmune and inflammatory diseases in the developed world. Healthy volunteer studies at the University of Nottingham showed therapeutic hookworm infection to be safe and well tolerated up to about 50 larvae, and then safety studies in people with airway hyperreactivity and inflammatory bowel disease raised no concern. Following a study in Argentina showing that people with MS have milder disease when they have a natural co-existing asymptomatic infection with intestinal parasites, we (Professor Pritchard, immunoparasitologist and myself) decided to test hookworm in MS, and for the first time used 25 larvae in a patient study. (more…)
Abuse and Neglect, Alzheimer's - Dementia, Autism, Medical Imaging, Mental Health Research, MRI, Multiple Sclerosis, Neurology, Technology / 23.12.2019 Interview with: Sebastian Magda, Ph.D Director of Science & Engineering CorTechs Labs, Inc What is the background for this study? Response: Previous studies have shown that the changes of brain structure volume and/or metabolic activity are associated with various neurological diseases. We have created an artificial intelligence clinical decision support tool based on brain volumetric and PET metabolic activity measurements as well as other clinical measurements. (more…)
Author Interviews, Biogen / 20.11.2019 Interview with: Aaron Deykin MD Vice President, Late Stage Clinical Development Biogen What data support the U.S. Food and Drug Administration’s (FDA) approval of VUMERITY™ (diroximel fumarate)? Response: The FDA approval of VUMERITY was based on a New Drug Application (NDA) submitted under the 505(b)(2) filing pathway. It included data from pharmacokinetic bridging studies comparing VUMERITY and TECFIDERA® (dimethyl fumarate) to establish bioequivalence, and relied, in part, on the FDA’s findings of safety and efficacy for TECFIDERA. The NDA submission also included interim exposure and safety findings from EVOLVE-MS-1, an ongoing, Phase 3, single-arm, open-label, two-year safety study evaluating VUMERITY in patients with relapsing-remitting multiple sclerosis (MS). Interim results from EVOLVE-MS-1 at the time of NDA submission included a low overall rate of VUMERITY treatment discontinuation due to adverse events (6.3 percent), and a rate of less than one percent of patients who discontinued VUMERITY treatment due to gastrointestinal (GI) adverse events. Additional exploratory efficacy endpoints in the ongoing EVOLVE-MS-1 study showed changes in clinical and radiological measures compared to baseline. (more…)
Author Interviews, Infections, Multiple Sclerosis, Neurological Disorders / 12.07.2019 Interview with: Prof. Dr. Patrick Küry Dept. of Neurology Heinrich-Heine-University Düsseldorf Germany What is the background for this study? How do these viruses in our DNA differ from others such as the herpes family of viruses? Response: The background of our current two published studies is elucidating the role of endogenous retroviruses such as the HERV-W in contributing to neurological disease initiation and progression. Our new paper in PNAS (Kremer et al., PNAS 2019) describes a novel axon damage scenario for Multiple Sclerosis (MS) in which a "toxic" protein called ENV from HERV-W instructs so called microglial cells in the human brain to attack and damage myelinated axons. Our second review article (Gruchot et al., Front Genet 2019) summarizes currently known effects on endogenous retroviruses exerted towards neural cells, that means cells other than the infiltrating immune cells. There is currently a shift of attention and research in the MS field in that resident neural cells such as oligodendrocytes, precursor cells, stem cells and microglial cells and their reactions are intensively investigated. HERVs are evolutionary acquired retroviruses (RNA viruses able to integrate into host DNA via reverse transcription from RNA to DNA) that were collected during evolution by our ancestors. Some of them remained in our genome (8% of our genome is HERV related) and in most cases appear to be non-functional, mutated or genetically silenced. A few of them, as for example HERV-W in MS or HERV-K in ALS, can apparently be activated, woken up so to say, and one of the mechanisms leading to activation might be an infection by Herpesviruses. Note that herpesviruses such as for example the Epstein Bar Virus (EBV) are long known suspected triggers of MS, however, a direct correlation could never be demonstrated. HERVs such as HERV-W might therefore constitute the missing link. (more…)
Author Interviews, McGill, Multiple Sclerosis, Neurology / 09.05.2019 Interview with: Douglas Arnold, MD The Montreal Neurological Institute & Hospital McGill University Montreal, QC, Canada What is the background for this study? Response: Diroximel fumarate (DRF) is a novel oral fumarate, with a distinct chemical structure that is being developed for relapsing forms of multiple sclerosis (MS). It is hypothesized that the distinct chemical structure of DRF may elicit less localized irritation in the gastrointestinal (GI) tract, potentially leading to improved GI tolerability. Diroximel fumarate is expected to have similar efficacy as dimethyl fumarate (marketed as TECFIDERA®), as both are converted to equivalent levels of monomethyl fumarate in the body. The EVOLVE-MS-1 study is primarily evaluating the safety of DRF and also exploring efficacy endpoints.   (more…)
Author Interviews / 07.05.2019 Interview with: Lana Zhovtis Ryserson, MD Assistant Professor, Department of Neurology NYU Langone Health What is the background for this study? What are the main findings? Response: Natalizumab is an effective therapy of relapsing remitting multiple sclerosis dosed at 300mg every 4 weeks. However it is associated with a potentially deadly infection - progressive multifocal leukoencephalopathy. In order to mitigate this risk, clinicians have adopted an approach of infusing the medication less frequently, a strategy which has become known as Extended Interval Dosing (EID). The TOUCH database is US mandatated risk evaluation and mitigation program which is the largest database available to assess PML risk for patients on EID schedule. Previous analysis of this database in 2017, showed a significant risk reduction of PML in patients utilizing extended interval dosing schedule. The aim of the current study was to update on this analysis with another year of data. (more…)
Author Interviews, Biomarkers, Multiple Sclerosis / 30.04.2019 Interview with: Prof. Bernhard Hemmer MD PhD Director of the Neurology Clinic Technische Universität München What is the background for this study? What are the main findings?  Response: The course of multiple sclerosis (MS) is still highly unpredictable and reliable markers to predict disability progression are largely missing. We found that patients with a high IgG Index, which means that the produce large amount of IgG within the CNS, have a higher risk of disease worsening during the first 4 years. I would consider patients with an elevated IgG index at a higher risk to run a more severe disease course. The marker could be used together with others to guide treatment decisions after multiple sclerosis diagnosis. (more…)
Author Interviews, Cleveland Clinic, Multiple Sclerosis, NEJM / 30.08.2018 Interview with: Robert J. Fox, MD, FAAN Principal Investigator | SPRINT-MS Trial Mellen Center for MS  |  Cleveland Clinic Cleveland, OH 44195 What is the background for this study? What are the main findings? Response: The current treatment options for progressive multiple sclerosis are very limited. The SPRINT-MS trial sought to obtain proof-of-concept evidence that ibudilast has beneficial activity in progressive multiple sclerosis. In a placebo-controlled, 96-week trial of 255 people living with progressive MS, treatment with ibudilast slowed the progression of brain atrophy (brain shrinkage) by 48% compared to placebo. Side-effects of ibudilast included gastrointestinal symptoms, headache, and depression.  (more…)
Author Interviews, JAMA, Neurology / 13.01.2018 Interview with: Fredrik Piehl MD PhD, prof. of Neurology Neuroimmunology Unit. Dept Clinical Neuroscience Neurology Dept. Karolinska University Hospital (Solna) Stockholm 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. (more…)
Author Interviews, Cognitive Issues, Multiple Sclerosis, NYU / 01.03.2017 Interview with: Leigh E. Charvet, PhD Associate Professor, Department of Neurology Department of Neurology New York University Langone Medical Center New York, NY 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. (more…)
Author Interviews, Lancet, Multiple Sclerosis, Neurological Disorders, Pharmacology / 12.02.2017 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 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. (more…)
Author Interviews, Biomarkers, JAMA, Multiple Sclerosis / 07.01.2017 Interview with: Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, Rotterdam 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. (more…)
Author Interviews, Immunotherapy, Multiple Sclerosis, NEJM, University Texas / 22.12.2016 Interview with: 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 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. (more…)
Author Interviews, Immunotherapy, Multiple Sclerosis / 22.11.2016 Interview with Ralph Kern, M.D. Senior vice president, Worldwide Medical Biogen 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. (more…)
Author Interviews, Multiple Sclerosis, PLoS, Vitamin D / 19.05.2016 Interview with: Ms Emily Weiss PhD student Centre for Population Health Sciences The University of Edinburgh What is the background for this study? What are the main findings?  Response: Vitamin D deficiency, a marker of low ultraviolet (UV) exposure, is common in Scotland; both have been shown to work independently as risk factors for multiple sclerosis (MS). Orkney, situated to the north of mainland Scotland has a very high prevalence of MS. We therefore wanted to understand how vitamin D in Orkney compares to mainland Scotland’s vitamin D, and also what may be determining vitamin D levels in Orkney. (more…)
Cleveland Clinic, Multiple Sclerosis / 16.09.2014

Jeffrey Cohen MD Department of Neurology Cleveland 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. (more…)
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 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). (more…)
Author Interviews, JAMA, Multiple Sclerosis / 05.09.2014

Jeffrey Cohen MD Department of Neurology Cleveland 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. (more…)
Author Interviews, BMJ, Multiple Sclerosis / 14.07.2014

Dr Nils Muhlert Wellcome Trust ISSF Research Fellow School of Psychology Cardiff 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. (more…)
Author Interviews, Multiple Sclerosis, Neurology / 03.04.2014

Jeppe Romme Christensen  MD PhD From the Danish Multiple Sclerosis Center Copenhagen University Hospital Hvidovre, Interview with: Jeppe Romme Christensen  MD PhD From the Danish Multiple Sclerosis Center Copenhagen University Hospital Hvidovre, Denmark. 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. (more…)
Author Interviews, Race/Ethnic Diversity / 08.05.2013 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. 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. (more…)