Author Interviews, JAMA, Multiple Sclerosis, Neurology / 15.06.2020

MedicalResearch.com Interview with: [caption id="attachment_54537" align="alignleft" width="200"]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 Prof. Constantinescu[/caption] 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 MedicalResearch.com: 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.
Author Interviews, Neurological Disorders, Neurology, Pain Research / 11.05.2020

MedicalResearch.com Interview with: [caption id="attachment_54158" align="alignleft" width="160"]Holly Yancy, DO Headache medicine specialist Phoenix, AZ Dr. Yancy[/caption] Holly Yancy, DO Headache medicine specialist Banner – University Medicine Neuroscience Institute Phoenix, AZ Dr. Yancy comments on the recent Neurology journal article on the potential impact of yoga on migraine.  MedicalResearch.com: What is the background for this study? How might yoga reduce migraine intensity or frequency?  Response: The authors of this trial have studied the benefits of yoga when added to medical management of episodic migraine. They expand on prior, smaller reports of the potential benefit of yoga and mindfulness to migraine patients with a well-designed study that shows yoga, as an adjunct to preventive medication, can lower the intensity, frequency and impact of migraines. Participants even used less abortive medication. The authors propose multiple potential mechanisms of action, including an increase in parasympathetic / decrease in sympathetic nervous system activity, decreased muscle tension, and stress management.
Author Interviews, Biogen, Neurological Disorders, Pharmaceutical Companies / 30.04.2020

MedicalResearch.com Interview with: [caption id="attachment_54059" align="alignleft" width="126"]Toby Ferguson, M.D., Ph.D. Vice President, Head Neuromuscular Development Unit Biogen Dr. Ferguson[/caption] Toby Ferguson, M.D., Ph.D. Vice President, Head Neuromuscular Development Unit Biogen MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by SMA, who is primarily affected and incidence? Response: Spinal muscular atrophy (SMA) is a rare, genetic, neuromuscular disease characterized by a loss of motor neurons in the spinal cord and lower brain stem that can result in severe, progressive muscle atrophy and weakness. Approximately one in 10,000 live births have a diagnosis of SMA. It is a leading genetic cause of infant mortality; however, people of all ages are impacted by the disease. More than three years ago, SPINRAZA (nusinersen) became the first FDA-approved treatment option for SMA. The DEVOTE study, which recently treated its first patient, is designed to evaluate the safety and potential for even greater efficacy of SPINRAZA when administered at a higher dose than currently approved for the treatment of SMA. The Phase 2/3 randomized, controlled, dose-escalating study will be conducted at approximately 50 sites around the world and aims to enroll individuals of all ages with SMA.
Author Interviews, Neurological Disorders, Parkinson's / 15.04.2020

MedicalResearch.com Interview with: [caption id="attachment_53918" align="alignleft" width="200"]Dr. Viviane Labrie, PhD Dr. Labrie[/caption] Dr. Viviane Labrie, PhD Dr. Labrie is an associate professor in Van Andel Institute’s Center for Neurodegenerative Science, where she studies Parkinson’s, Alzheimer’s and other neurological diseases. MedicalResearch.com: What is the background for this study? Response: One of the most puzzling and persistent mysteries in neuroscience has been why some people are “right-brained” while others are “left-brained.” The two sides of the brain have different jobs. The left side is analytic and problem-solving, while the right side manages creativity and artistic talents. But despite their differences, the two sides are composed of the same cell types — essentially, brain neurons and their support cells. In this study, we sought to understand how it is possible for these cells to behave completely differently depending on what hemisphere they’re located in.  We also wanted to examine the reasons behind asymmetry in Parkinson’s disease; that is, why Parkinson’s symptoms typically start on one side of the body before the other. This asymmetry in neurodegeneration and symptoms in patients is one of the biggest unsolved puzzles in the Parkinson’s disease field — why do brain cells in one hemisphere begin dying before brain cells in the other hemisphere?
Abuse and Neglect, Alzheimer's - Dementia, Autism, Medical Imaging, Mental Health Research, MRI, Multiple Sclerosis, Neurology, Technology / 23.12.2019

MedicalResearch.com Interview with: [caption id="attachment_52575" align="alignleft" width="156"]Sebastian Magda, Ph.D Director of Science & Engineering CorTechs Labs, Inc Dr. Sebastian Magda[/caption] Sebastian Magda, Ph.D Director of Science & Engineering CorTechs Labs, Inc MedicalResearch.com: 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.
Author Interviews, Epilepsy / 19.12.2019

MedicalResearch.com Interview with: [caption id="attachment_52529" align="alignleft" width="160"]Steve S. Chung MD Epilepsy Neurology Banner University Medical Center University of Arizona, Phoenix, AZ Dr. Chung[/caption] Steve S. Chung MD Epilepsy Neurology Banner University Medical Center University of Arizona, Phoenix, AZ MedicalResearch.com: What is the background for this study? Response: Prior studies have shown that midazolam nasal spray (MDZ-NS) is superior to placebo in providing rapid, sustained seizure control and a favorable safety profile when administered to patients experiencing seizure clusters, a type of seizure emergency impacting an estimated 150,000 patients in the U.S. with uncontrolled epilepsy. To explore the influence of concomitant antiepileptic drugs (AEDs) on treatment outcomes, we conducted a post hoc analysis of a Phase III trial to evaluate the tolerability and efficacy of midazolam nasal spray in patients 12 years of age and older with seizure clusters, according to concomitant enzyme-inducing AED (EIAED)/non-enzyme-inducing AED (NEIAED) status and by the number of concomitant AEDs.
Author Interviews, Epilepsy / 19.12.2019

MedicalResearch.com Interview with: [caption id="attachment_52524" align="alignleft" width="200"]Eun Jung Choi, MD, PhD; Senior Director, New Product Launch, Neurology UCB Dr. Eun Jung Choi[/caption] Eun Jung Choi, MD, PhD; Senior Director, New Product Launch, Neurology UCB MedicalResearch.com: What is the background for this study? Response: Patients experiencing seizure clusters, a type of seizure emergency impacting an estimated 150,000 patients in the U.S. with uncontrolled epilepsy, are at risk for potentially serious consequences including hospitalization, mortality, physical injury, neurological damage, and status epilepticus. Although unmet needs of seizure clusters are intuitively well accepted, the burden of seizure clusters has not been well characterized and evaluated in a systemic matter. As a result, the seizure cluster patients are overlooked, and burden of seizure clusters is under-recognized. So we systematically assessed the clinical, humanistic, and economic burden associated with seizure clusters to provide the comprehensive body of evidence about burden of seizure clusters.
Author Interviews, Epilepsy, NEJM, NIH / 11.12.2019

MedicalResearch.com Interview with: [caption id="attachment_52433" align="alignleft" width="160"]Robin Conwit, M.D Program Director, Division of Clinical Research NIH: National Institute of Neurological Disorders and Stroke Dr. Conwit[/caption] Robin Conwit, M.D Program Director, Division of Clinical Research NIH: National Institute of Neurological Disorders and Stroke MedicalResearch.com: What is the background for this study? Response: Approximately one-third of patients with intractable status epilepticus do not respond to benzodiazepines, often the first line medications given in the emergency department, leaving doctors to decide among three commonly prescribed anti-convulsants. In this study all of the anti-convulsants were equally effective. The trial gives doctors a way to clear the air of arguments that one of these drugs works any better than the others, or that any one of them is a lot safer.  It gives doctors a reason to choose a dosing strategy in status epilepticus for levetiracetam, which has otherwise been controversial and non-standard.  
Author Interviews, Lipids, NEJM, Neurological Disorders, Stroke / 18.11.2019

MedicalResearch.com Interview with: [caption id="attachment_52201" align="alignleft" width="200"]Dr-Pierre Amarenco Dr. Pierre Amarenco[/caption] Pierre Amarenco, MD Professor and Chairman Paris University, Paris, France INSERM Department of Neurology and Stroke Centre Bichat Hospital Paris, France MedicalResearch.com: What is the background for this study? Response: The rationale of the Treat Stroke to target trial was that after we published the SPARCL trial in 2006 (atorvastatin 80 mg/day vs placebo in patients with stroke) which showed a 16% relative risk reduction of recurrent stroke, we performed several pre specified and post hoc analyses, showing that in SPARCL patients randomized with "atherosclerotic disease" the risk reduction for the primary endpoint was much higher (33%), and in in patients achieving a LDL cholesterol of less than 70 mg/dL as compared to those achieving a LDL cholesterol 100 mg/dL or higher, the risk reduction was 28%. Therefore to confirm this findings, we designed the TST trial, which was an investigator initiated trial funded by the french ministry of health,  and enrolled patients with an ischemic stroke due to atherosclerotic stenosis and randomized them to either a target LDL cholesterol of less than 70 mg/dL or a target LDL cholesterol of 90 to 110 mg/dL. To achieve these goals, the investigators could use any statin available on the market, and titrate the dosage of the statin to get to the assigned target. They could also use ezetimibe on top of statin therapy if a high dosage of statin was not sufficient to get to the target level assigned by randomization.
Author Interviews, Epilepsy, Nutrition / 23.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50377" align="alignleft" width="168"]Geoffrey W. Abbott PhD Department of Physiology and Biophysics, Bioelectricity Laboratory, School of Medicine, University of California Dr. Abbott[/caption] Geoffrey W. Abbott PhD Department of Physiology and Biophysics, Bioelectricity Laboratory, School of Medicine, University of California MedicalResearch.com: What is the background for this study? Response: The main focus of my laboratory is the study of potassium ion channels - proteins that coordinate electrical activity in all organisms. When human potassium channels do not function properly, it can result in pathologically discordant electrical activity, and diseases such as cardiac arrhythmia, myotonia, and epilepsy - depending on whether the affected potassium channel is in the heart, skeletal muscle or brain, for example. T here are existing drugs that directly regulate ion channels for therapeutic benefits, including one - retigabine - that opens neuronal potassium channels in the KCNQ family, to treat epilepsy. Retigabine causes side effects including turning the skin blue, and was withdrawn from clinical use in 2017. Retigabine may make a comeback because a form of epilepsy was recently discovered, arising from mutations in the KCNQ2 gene, that is associated with severe developmental delay and seizures. In my lab, we are interested in discovering new therapeutic agents that might more safely fix dysfunction in KCNQ2 and other potassium channels. We turned to plants as a possible source of compounds. We are interested both in explaining the underlying mechanism of traditional botanical medicines, and also discovering unanticipated therapeutic chemicals synthesized naturally by plants. 
Author Interviews, Infections, Multiple Sclerosis, Neurological Disorders / 12.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50243" align="alignleft" width="170"]Prof. Dr. Patrick Küry Dept. of Neurology Heinrich-Heine-University Düsseldorf Germany Prof. Küry[/caption] Prof. Dr. Patrick Küry Dept. of Neurology Heinrich-Heine-University Düsseldorf Germany MedicalResearch.com: 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.
ALS, Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, Multiple Sclerosis / 27.06.2019

MedicalResearch.com Interview with: [caption id="attachment_50018" align="alignleft" width="200"]Charlotte E. Teunissen, Prof. Teunissen[/caption] Charlotte E. Teunissen, PhD Neurochemistry Laboratory, Department of Clinical Chemistry VU University Medical Centre, Neuroscience Campus Amsterdam Amsterdam, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Several reports have shown increased in NfL in various neurological disorders, separately. We wanted to know how the levels are in these disorders relative to each other. Moreover, some reports showed absence of age effects in Multiple Sclerosis (MS) patients, which is normally present in controls. So, we thought that it would be good to study age effects in a large group of controls, and if these effects are absent in other diseases, similarly as in MS.
Author Interviews, Epilepsy, FDA / 29.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49403" align="alignleft" width="200"]Dr. Steven S. Chung, MDExecutive Director and Program ChairNeuroscience Institute and Director of the Epilepsy ProgramBanner – University Medical Center Dr. Chung[/caption] Dr. Steven S. Chung, MD Executive Director and Program Chair Neuroscience Institute and Director of the Epilepsy Program Banner – University Medical Center MedicalResearch.com: What is the background for this study? How is Nayzilam different from other treatments for epilepsy? Who/How is it administered?  Response: NAYZILAM is the first medication and only FDA-approved nasal option for treating seizure clusters. NAYZILAM allows for administration by a non-healthcare professional to patients when a seizure cluster occurs, which could provide significant value to patients who currently have limited treatment options for SC. The effectiveness of NAYZILAM was established in a randomized, double-blind, placebo-controlled trial (Study 1; NCT 01390220). Study 1 was conducted in two phases: an open-label Test Dose Phase followed by a randomized, double-blind, placebo-controlled, Comparative Phase. In the Test Dose Phase, tolerability was assessed in 292 patients. Patients were excluded from participation in the Comparative Phase if they failed to meet pre-defined blood pressure, heart rate, sedation, electrocardiogram, and peripheral oxygen saturation criteria. In the Comparative Phase, 201 patients treated a single seizure cluster episode in an outpatient setting. Numerical differences in favor of NAYZILAM were observed on each of the components of the treatment success responder definition; termination of seizure(s) within 10 minutes after initial dose of study drug (80.6 versus 70.1%) and the absence of seizure recurrence between 10 minutes and 6 hours after the initial dose of study drug (58.2 versus 37.3%). Study 1 also evaluated the occurrence and time to next seizure after the initial blinded dose of study drug. A smaller proportion of NAYZILAM-treated patients experienced the next seizure within 24 hours after the initial blinded dose of study drug (37.3% versus 46.3%). NAYZILAM-treated patients experienced a statistically longer time-to-next-seizure than the placebo group.  
Author Interviews, Brain Injury, Neurological Disorders, Neurology, Stroke / 12.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49129" align="alignleft" width="128"]Thomas M Van Vleet PhDPosit Science  Dr. Van Vleet[/caption] Thomas M Van Vleet PhD Posit Science  Dr. Tom Van Vleet,  presented results on a common symptom of stroke and acquired brain injury (hemi-spatial neglect) at the American Academy of Neurology May 2019 MedicalResearch.com: What makes this study newsworthy? Response For the first time ever a highly-scalable intervention — computerized brain training (BrainHQ made by Posit Science) —was found to improve symptoms of hemi-spatial neglect, which is a common and often intractable and debilitating problem after stroke or other acquired brain injury. MedicalResearch.com: What can you tell us about the medical condition (hemi-spatial neglect) investigated in this study? Response About a third of patients with a brain injury exhibit a complex and debilitating array of neurological deficits known as the “neglect syndrome” (sometimes called, “hemi-spatial neglect” or “neglect”). The most apparent symptom of neglect is the inability of patients to efficiently process information on the side of space opposite the injury; often completely missing relevant events without awareness. As a result, patients often fail to adopt compensatory strategies or respond to other conventional rehabilitation protocols. The cost is significant, as patients with neglect experience longer hospital stays and have higher requirements for assistance, including greater skilled nursing home placements relative to patients with similar extent of brain injury without neglect. To date, there’s been no broadly-applicable and highly-scalable intervention for addressing neglect. An alarming reality given the increasing cost of stroke, which is currently estimated to exceed $34 billion per annum
Author Interviews, McGill, Multiple Sclerosis, Neurology / 09.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49095" align="alignleft" width="146"]Douglas Arnold, MDThe Montreal Neurological Institute & HospitalMcGill University Montreal, QC, Canada Dr. Arnold[/caption] Douglas Arnold, MD The Montreal Neurological Institute & Hospital McGill University Montreal, QC, Canada MedicalResearch.com: 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.  
Alzheimer's - Dementia, Author Interviews, Biomarkers, Neurological Disorders, Neurology, University of Pennsylvania / 08.05.2019

MedicalResearch.com Interview with: Lauren McCollum, MDCognitive and Behavioral Neurology FellowPenn Memory Center / Cognitive Neurology DivisionLauren McCollum, MD Cognitive and Behavioral Neurology Fellow Penn Memory Center / Cognitive Neurology Division MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s Disease (AD) is a heterogenous condition, with considerable variability in cognitive symptoms and progression rates. One major reason for this heterogeneity is “mixed pathology,” – i.e., both AD- and non-AD pathology. Examples of non-AD pathology include cerebrovascular disease (CVD), Lewy Bodies, and TDP-43. Pathologically, Alzheimer’s Disease is defined by characteristic amyloid plaques and neurofibrillary tangles, which can be assessed for in living patients with CSF- or PET-based biomarkers for amyloid and tau, respectively. Classically, amyloid deposition begins years or even decades before pathologic tau accumulation, which is in turn associated with brain atrophy and cognitive decline. The recently developed NIA-AA “ATN” research framework allows for the classification of individuals with regard to 3 binary biomarkers: Amyloid (A), Tau (T), and Neurodegeneration (N). An individual’s ATN biomarker status indicates where along the “Alzheimer’s Disease continuum” they lie. Additionally, some ATN statuses are on the “typical AD” continuum, while others are not. Research has shown that 15-30% of cognitively normal older adults have elevated amyloid. It stands to reason that some portion of cognitively impaired individuals with elevated amyloid and neurodegeneration have something other than AD driving their neuronal injury. Within the context of the ATN research framework, this subset of people is the A+T-N+ group (i.e., people who have elevated amyloid and neurodegeneration, but are tau-negative), as amyloid alone (that is, amyloid without tau) is not thought to cause significant cognitive impairment or brain atrophy. Our hypothesis was that, compared to A+T+N+ (a set of typical-AD biomarkers), A+T-N+ have cognitive and neuroimaging profiles that deviate from a typical Alzheimer’s Disease pattern – i.e., with less memory loss and less atrophy in AD-signature regions – and may have biomarkers suggestive of alternate non-AD pathologies [e.g., white matter hyperintensities (WMHs), a marker of CVD].
Author Interviews, Biomarkers, Multiple Sclerosis / 30.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48900" align="alignleft" width="140"]Prof. Bernhard Hemmer MD PhDDirector of the Neurology ClinicTechnische Universität München Prof. Hemmer[/caption] Prof. Bernhard Hemmer MD PhD Director of the Neurology Clinic Technische Universität München  MedicalResearch.com: 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.
Author Interviews, Nature, Neurological Disorders, Nursing / 18.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48691" align="alignleft" width="200"]Dr-Elsa F. Fouragnan Dr. Fouragnan[/caption] Elsa F. Fouragnan PhD School of Psychology (Faculty of Health and Human Sciences) University of Plymouth MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Counterfactual thinking is a psychological process that involves the tendency to create possible alternatives to life events that are currently happening. It is very important because it gives us the ability to switch away from uninteresting activities if better ones become available. For example, if you are working or doing the housework, you may be thinking about gardening or watching a movie later. As soon as your duties are finished, you may engage in these more exciting activities. In our study, macaque monkeys were tasked to find treats under several colored cups (on a screen). Some of these cups were better than others but were not always available, thus the animals had to retain what they had learnt about the good cups in case they became available again. We found that a frontal part of the brain called the anterior cingulate cortex was responsible for tracking which cups were the best in order to efficiently switch to them if the opportunity arose. If this part of the brain was not functioning properly, then animals were stuck in non-optimal choices. To reveal the causal role of the anterior cingulate cortex, we used a new neurostimulation method called low-intensity repetitive ultrasound to modulates activity in this part of the brain with millimetre accuracy.
Author Interviews, Epilepsy, Genetic Research, JAMA, Pediatrics / 12.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48481" align="alignleft" width="200"]Dr. Ahmad Abou Tayoun, PhDClinical Molecular GeneticistDirector of the Genetics LaboratoryAl Jalila Children’sUnited Arab Emirates Dr. Abou Tayoun[/caption] Dr. Ahmad Abou Tayoun, PhD Clinical Molecular Geneticist Director of the Genetics Laboratory Al Jalila Children’s United Arab Emirates MedicalResearch.com: What is the background for this study?   Response: In this study, we provide data in favor of using an exome-based testing approach, where parental samples can be readily accessible, for early onset epilepsy patients. The exome test includes all coding genes in the human genome. Although we perform exome sequencing on those patients, we demonstrate that a first tier analysis should include targeted interpretation of ~100 genes strongly associated with the disease. This analysis provides diagnoses in ~11% of the patients. Follow up parental testing on a limited number of patients (n=15) that had inconclusive results, revealed de novo (new mutations) variant status, leading to upgrade to positive reports in 7 patients and adding ~5% to the overall diagnostic yield.
Author Interviews, Depression, Exercise - Fitness, JAMA, Parkinson's / 10.04.2019

MedicalResearch.com Interview with: Dr. Jojo Kwok  R.N., BN(Hons), MPH, Ph.D. School of Nursing, Li Ka Shing Faculty of Medicine The University of Hong Kong MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Before the study, we knew that mind-body exercises such as yoga and stretching improves the physical health of patients with Parkinson’s disease (PD), however the benefits to their mental health was not known. This study concludes that mindfulness yoga alleviates psychological distress, improves spiritual well-being and quality of life, not to mention motor symptoms and mobility. When it comes to managing the stress and symptoms of Parkinson Disease, what is exciting, is that yoga has now been proven to be a better strategy than just stretching. Yoga draws together body, mind and spirit through mindful practice of 1) yoga posture, 2) breathing and 3) meditation. These form the three core components of our Mindfulness Yoga Program. Mindfulness is non-judgemental awareness of the present moment - of one’s physical sensations and thoughts, be they positive or negative. By adopting a mind-body approach, patients are much better positioned to reframe their illness journey than through physical training alone. By learning to relate non-judgmentally to their physical symptoms and emotions, they develop new coping skills that cultivate openness, acceptance and resilience to these symptoms. They feel better. 
ALS, Author Interviews, Statins / 15.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47512" align="alignleft" width="128"]Alastair J. Noyce MD, PhD  Preventive Neurology Unit, Wolfson Institute of Preventive Medicine Queen Mary University of London, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology, London UK Dr. Noyce[/caption] Alastair J. Noyce MD, PhD Preventive Neurology Unit, Wolfson Institute of Preventive Medicine Queen Mary University of London, Department of Clinical and Movement Neurosciences, University College London, Institute of Neurology, London UK MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Amyotrophic lateral sclerosis (ALS) or motor neurone disease (MND) is a relentlessly progressive disorder that affects nerves which supply muscles. Over time the nerves die, leading to limb weakness, speech and swallowing problems, and ultimately breathing problems. Patients die on average 3-5 after diagnosis. There is no cure and the underlying disease processes are only understood in part. In this study, we adopted a large-scale approach to exploring causal risk factors for ALS. Causality is important because it implies that if one could modify or induce a change in a risk factor, one would observe a change in the risk of ALS. Observational studies struggle to prove causality definitely. Associations in observational studies can arise because: 1) the risk factor truly changes risk of ALS; or 2) something about ALS changes one’s exposure to the risk factor; or 3) the presence of another factor, which may or may not be known, can induce an association between a risk factor and ALS. Unless scenario 1 represents the truth, then changing the risk factor will not have any effect on risk of ALS. We used a proxy-based approach, known as Mendelian randomisation, to assess hundreds of possible risk factors for ALS for evidence of causality. What emerged from this was a very clear signal linking LDL cholesterol to risk of ALS.
Aging, Author Interviews, Neurological Disorders / 24.01.2019

MedicalResearch.com Interview with: [caption id="attachment_47107" align="alignleft" width="133"]Rachael D. Seidler, PhD Professor, Applied Physiology & Kinesiology University of Florida Dr. Seidler[/caption] Rachael D. Seidler, PhD Professor, Applied Physiology & Kinesiology University of Florida MedicalResearch.com: What is the background for this study? Response: There is accumulating evidence that spaceflight impacts the human brain: the brain is shifted higher within the skull and there are some regions of gray matter increases and decreases. To date, no studies have looked at the impact of spaceflight on human brain white matter pathways. Rodents flown in space show decreased myelination of white matter pathways. Here, we analyzed brain MRI scans pre and post spaceflight to quantify fluid shifts and white matter changes.
ALS, Author Interviews, Brigham & Women's - Harvard, Cognitive Issues, JAMA, Multiple Sclerosis / 08.01.2019

MedicalResearch.com Interview with: [caption id="attachment_46832" align="alignleft" width="200"]Michael Fralick, MD, FRCPC, SM, PhD (Cand) Clinical Associate, General Internal Medicine, St Michael’s Hospital Phillipson Scholar, Clinician Scientist Program, University of Toronto  PhD Candidate, IHPME, University of Toronto Affiliated Faculty, Program On Regulation, Therapeutics, And Law, Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital, Harvard University Dr. Fralick[/caption] Michael Fralick, MD, FRCPC, SM, PhD (Cand) Clinical Associate, General Internal Medicine St Michael’s Hospital Phillipson Scholar, Clinician Scientist Program, University of Toronto PhD Candidate, IHPME, University of Toronto Affiliated Faculty, Program On Regulation, Therapeutics, And Law, Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital, Harvard University MedicalResearch.com: What is the background for this study? What are the main findings? Response: This medication is a pill that combines two ingredients: dextromethorphan (the active ingredient in cough syrup) and quinidine (used to increase the concentration of dextromethorphan). The medication was primarily studied and evaluated in patients with amyotrophic lateral sclerosis (ALS)   or (multiple sclerosis) MS, but anecdotal evidence suggested it was being prescribed to patients with dementia. We used data from two nationwide healthcare databases to understand how the medication was being used in routine care.
Author Interviews, Immunotherapy, Multiple Sclerosis / 27.11.2018

MedicalResearch.com Interview with: [caption id="attachment_46225" align="alignleft" width="142"]Dietmar P. Berger, MD, PhD Head of Global R&D Atara Biotherapeutic Dr. Berger[/caption] Dietmar P. Berger, MD, PhD Head of Global R&D Atara Biotherapeutic MedicalResearch.com: What is the background for this study? Response: Epstein-Barr virus (EBV) is present in B lymphocytes, plasma cells and epithelial cells of over 95% of individuals over the age of 40.  Multiple studies have shown that nearly all patients with Multiple Sclerosis (MS) are EBV positive, including a recent presentation at the 2018 ECTRIMS Congress in Berlin that showed 100% of MS patients are positive for EBV (Ruprecht et. al). Current B cell directed therapies such as anti-CD20 therapies have demonstrated an effect on  Multiple Sclerosis activity. These therapies work by depleting B cells including those infected by EBV. Our belief is that loss of EBV-specific T cell function (e.g., T cell exhaustion) occurs in patients who develop Multiple Sclerosis, which results in the accumulation of EBV infected B and plasma cells in the CNS leading to the autoreactive immune cycle seen in MS patients. The increasing evidence of a link between EBV infection and the development of MS led to the initiation of a Phase 1 study to investigate the use of an autologous T-cell immunotherapy (ATA190) to selectively target and deplete EBV infected cells in patients with progressive MS. As T cell immunotherapies (like ATA190) are designed to penetrate the central nervous system, this approach was felt to be particularly useful in  Multiple Sclerosis where the inflammatory response and infected B lymphocytes and plasma cells are inaccessible inside the CNS to the vast majority of classic targeted agents.
Alzheimer's - Dementia, Author Interviews, Coffee, Parkinson's / 14.11.2018

MedicalResearch.com Interview with: Donald Weaver, PhD, MD, FRCPC, FCAHS Senior Scientist and Director, Research Institute Krembil Research Institute University Health Network Toronto, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: First, we are seeking novel molecules that might have usefulness in the treatment of Alzheimer’s disease (AD). Since Mother Nature is a superb chemist, natural products are an ideal place to start looking for possible therapeutics. There is a long history (penicillin, digitalis …) of drugs identified from natural product sources. Moreover, in earlier work by us, we have shown that other natural products extracted from maple syrup have possible therapeutic efficacy against AD. Therefore, it was logical for us to look at extracts of coffee. We see similarities between maple syrup and coffee. In both of these natural products, the plant derived material (i.e. the coffee bean, or sap from maple syrup) is initially boiled or roasted prior to its use; thus, it is not a direct simple plant product, but one that has been heated (boiled or roasted). We suspect that the heating process “does more chemistry” enabling the generation of new molecules from the plant derived materials. In our study we show that a class of compounds (phenylindanes) from roasted coffee has the ability to inhibit the misfolding of two proteins (beta-amyloid, tau) whose misfolding and aggregation (“clumping”) is implicated in the disease process of AD. Second, as described below, there is already epidemiological evidence that coffee consumption may offer some protective effects against Alzheimer’s disease and Parkinson’s disease (PD), so by looking at the constituents of coffee for chemicals that might block the clumping of beta-amyloid and/or tau, was an attempt to seek a molecular link explaining the epidemiology.
Author Interviews, Gastrointestinal Disease, Parkinson's / 01.11.2018

MedicalResearch.com Interview with: [caption id="attachment_45629" align="alignleft" width="200"]Viviane Labrie, Ph.D. Assistant Professor, Center for Neurodegenerative Science Van Andel Research Institute Grand Rapids, Michigan Dr. Labrie[/caption] Viviane Labrie, Ph.D. Assistant Professor Center for Neurodegenerative Science Van Andel Research Institute Grand Rapids, Michigan MedicalResearch.com: What is the background for this study? Response: Our lab has an interest in the early events and initiation of neurodegenerative diseases. Parkinson’s disease for a long time was thought to be a movement disorder driven by the destruction of dopamine neurons in a specific area of the brain, the substantia nigra. In the last 10 years it has become evident that Parkinson’s disease is not just a movement disorder but hosts a whole range of non-motor systems. One of the most common non-motor symptoms in Parkinson’s patients is issues with the gastrointestinal (GI) tract. GI symptoms often occur early in Parkinson’s disease; for many patients, GI symptoms precede the onset of motor symptoms by as many as 2 decades. Moreover, the GI is not only involved in the early signs of Parkinson’s but has been proposed to be a place in the body where Parkinson’s disease begins. The hallmark pathology of Parkinson’s disease in the brain is Lewy bodies, which contains a clumped form of a protein called alpha-synuclein. There is evidence that Parkinson’s disease pathology, this clumped alpha-synuclein protein, is detectable in the GI tract, even many years before the onset of Parkinson’s motor symptoms. Clumped alpha-synuclein is also capable of traveling across nerve cells. There is evidence that clumped alpha-synuclein can travel up the nerve that connects the GI tract to the brain and enter the brain. This could be disastrous because clumped alpha-synuclein can seed and spread in the brain, which has neurotoxic effects and can eventually lead to Parkinson’s disease. In fact, in the brain of Parkinson’s patients, one of the first places where alpha-synuclein clumps are detected is at the terminal where the gut nerve connects to the brain, and this pathology advances from this point to other brain areas as the disease progresses. This intriguing connection of the GI tract to the early processes of Parkinson’s disease had us interested in trying to understand how the gut could be involved in triggering Parkinson’s. But the GI tract is a very big place, and we first asked ourselves, where should we look to better understand GI involvement in Parkinson’s disease?
Author Interviews, JAMA, Neurology, Outcomes & Safety, Parkinson's, Pharmacology, University of Pennsylvania / 04.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45003" align="alignleft" width="148"]Allison W. Willis, MD, MS Assistant Professor of Neurology Assistant Professor of Biostatistics and Epidemiology Senior Fellow, Leonard Davis Institute Senior Scholar, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania School of Medicine Dr. Willis[/caption] Allison W. Willis, MD, MS Assistant Professor of Neurology Assistant Professor of Biostatistics and Epidemiology Senior Fellow, Leonard Davis Institute Senior Scholar, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was motivated by my own experiences as a neurologist-neuroscientist. I care for Parkinson disease patients, and over the year, have had numerous instances in which a person was taking a medication that could interact with their Parkinson disease medications, or could worsen their PD symptoms.
ALS, Author Interviews, Pharmaceutical Companies / 27.09.2018

MedicalResearch.com Interview with: RetrotopeRobert J Molinari, Ph.D. President and CEO Retrotope, Inc.   MedicalResearch.com: What is the background for this study? How does RT001 differ from other treatments for neurodegenerative diseases?  Response: Lipid peroxidation in critical cell and mitochondrial membranes represents a common pathway of cell death in many neurodegenerative diseases, regardless of the initiating trigger of original damage, e.g. aberrant gene expression, misfolded proteins such as tau and amyloid, environmental insults, etc. This hypothesis was supported by work showing that stabilizing lipids (using virtually indistinguishable isotopic variants of the original dietary molecules) was able to mitigate disease-related cell dysfunction, and reverse disease in a variety of animal models, and more recently, in human patients enrolled in clinical trials. It has been known for decades that lipid peroxidation detritus of oxidized membrane fats are present in most all diseases of degeneration and aging, including Alzheimer’s disease, Parkinson’s disease, atherosclerosis, ALS, Huntington’s, and fatal inborn genetic errors resulting in neurodegenerative diseases (among others). The hypothesis that controlling such oxidation could provide therapeutic benefit was abandoned when numerous formal trials of classical antioxidants, e.g. Co-enzyme Q, Vitamin E, and others failed to provide meaningful benefit. We believed that the antioxidant mechanism used to attempt control of the membrane oxidation was flawed, but that the target itself was correct. Indeed, by using a new class of oral drugs that are lipids fortified against damage at the key susceptible bonds, we observed reduction in lipid peroxidation damage that halted, and even reversed neurodegenerative disease progression. Dosed in amounts and forms similar to omega 3 and 6 supplements, these drugs exhibited profound disease modification across a broad range of diseases in animal models, placebo controlled- and open label- human trials.
Author Interviews, Exercise - Fitness, JAMA, Neurology, Parkinson's / 23.09.2018

MedicalResearch.com Interview with: Fudi Wang, M.D., Ph.D. Qiushi Chair Professor Nutrition Discovery Innovation Center School of Public Health/School of Medicine Zhejiang University Hangzhou 310058, ChinaFudi Wang, M.D., Ph.D. Qiushi Chair Professor Nutrition Discovery Innovation Center School of Public Health/School of Medicine Zhejiang University Hangzhou  China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Parkinson disease (PD) is the second most common neurodegenerative disease affecting approximately 10 million people around the world. To date, the cause of PD remains poorly understood. It is reported that 90% PD cases have no identifiable genetic cause. What’s worse, few therapeutic advances for the treatment of PD have been made in the past decades. Nevertheless, growing prospective longitudinal studies shed lights on the potential beneficial effect of lifestyle factors on reducing the risk of developing Parkinson disease. In this study, we performed a a dose-response meta-analysis of more than half a million participants. We found that physical activity, particularly moderate to vigorous physical activity, could significantly reduce PD risk.
Author Interviews, Cleveland Clinic, Multiple Sclerosis, NEJM / 30.08.2018

MedicalResearch.com Interview with: [caption id="attachment_44175" align="alignleft" width="159"]Robert J. Fox, MD, FAAN Principal Investigator | SPRINT-MS Trial Mellen Center for MS  |  Cleveland Clinic Cleveland, OH 44195   Dr. Fox[/caption] Robert J. Fox, MD, FAAN Principal Investigator | SPRINT-MS Trial Mellen Center for MS  |  Cleveland Clinic Cleveland, OH 44195  MedicalResearch.com: 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.