Author Interviews, Beth Israel Deaconess, JAMA, Neurological Disorders / 06.07.2016

MedicalResearch.com Interview with: Samuel Frank, MD Director of the Huntington’s Disease Society of America Center of Excellence Beth Israel Deaconess Medical Center Boston, MA 02215 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Huntington Disease is a hereditary, progressive neurodegenerative disease characterized by involuntary movements (chorea and dystonia), cognitive dysfunction and psychiatric symptoms. Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism, increases active metabolite half-lives leading to stable systemic exposure. We found that deutetrabenazine significantly reduces chorea. There was also an overall improvement in participants' condition based on patient and clinician measures and improvement in a quality of life measure. There was no worsening, but also no improvement in balance. The improvements in Huntington Disease were seen with a remarkably good safety and tolerability profile. (more…)
Author Interviews, Microbiome, Multiple Sclerosis, Nutrition, Science / 02.07.2016

MedicalResearch.com Interview with: Ashutosh K Mangalam PhD Assistant Professor Department of Pathology University of Iowa Iowa City, IA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Every human carries trillions of bacteria in their gut (gut microbiome) and recent advances in research indicate that these tiny passengers play an important role in our overall health maintenance. Having evolved over the time span of millions of years with the gut microbiome, they keep us healthy in multiple ways such as fermentation and absorption of undigested carbohydrates, synthesis of some vitamins, metabolism of bile acids etc. However, new research suggests that gut microbiome, also regulating our body’s defense system. It is hypothesized that a diverse gut microbiome is good for our health and perturbations in this might predispose us to disease development. Therefore, we asked whether multiple sclerosis (MS) patients have a gut microbiome which is distinct from healthy individuals. We collected fecal samples from MS patients and healthy controls and performed microbiome analysis. I have recently moved to UI but the entire study was completed at Mayo Clinic Rochester. This study involved a big team comprised of neurologist, gastroenterologist, bioinformatician, system biologist and study coordinators. We found that  multiple sclerosis patients indeed have a gut microbiome which is different from what is observed in healthy people. We identified certain bacteria which are increased or decreased in the gut of patients with multiple sclerosis compared to healthy controls. (more…)
Author Interviews, Emergency Care, Neurological Disorders, NYU, Pain Research / 30.06.2016

MedicalResearch.com Interview with: Mia Minen, MD, MPH Assistant Professor of Neurology NYU Langone Medical Center MedicalResearch.com Editor’s note: The American Headache Society has issued new guidelines on “The Management of Adults With Acute Migraine in the Emergency Department” (1,2) Dr. Minen, Director of Headache Services at NYU Langone Medical Center, discusses these new guidelines below. MedicalResearch.com: What is the background for these new guidelines? How common/severe is the issue of migraine or headache presentation to the ER? Dr. Minen: These guidelines were needed because previous research shows that there are about 1.2. million visits to the emergency department (ED) each year for migraine, and over 25 different medications are sometimes used for treatment. Many of these medications don’t have evidence-based data to back their usage, and opioids are especially likely to be prescribed in between 60 and 70 percent of these cases, despite their lack of efficacy and risks. The American Headache Society convened an expert panel to review the existing evidence on all the medications used to treat migraines in the ED, and we developed these new treatment guidelines. (more…)
Author Interviews, MRI, Neurological Disorders, Neurology, NIH, Stroke / 22.06.2016

MedicalResearch.com Interview with: Dr. Richard Leigh MD Neuro Vascular Brain Imaging Unit National Institute of Neurological Disorders and Stroke National Institutes of Health, Bethesda, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who suffer an ischemic stroke have limited treatment options. One of the reasons for this is that our treatments can sometimes make the stroke worse by transforming the ischemic stroke into a hemorrhagic stroke. In our study we identified a new piece of information that we can extract from the patient’s MRI scan that informs us on the risk of having a hemorrhage. (more…)
ADHD, Author Interviews, JAMA, Mental Health Research, Neurological Disorders / 11.06.2016

MedicalResearch.com Interview with: Katya Rubia, PhD Department of Child and Adolescent Psychiatry Institute of Psychiatry, Psychology, and Neuroscience King’s College London London, England MedicalResearch.com:  What are the main findings? Dr. Rubia: ADHD and OCD patients both suffer from poor inhibitory control and in both disorders this has been associated with structural and functional deficits in fronto-striatal networks. However, it is not clear to what extent the two disorders differ in their underlying neural substrates. This study therefore conducted a meta-analysis of all published whole brain structural and functional MRI studies of inhibitory control in both disorders. MedicalResearch.com: What are the main findings? Dr. Rubia: The main findings are that ADHD and OCD patients differ quite fundamentally in their structural and functional brain abnormalities. OCD patients have enlarged volume in basal ganglia and insula, while ADHD patients have reduced volumes in these regions. In fMRI, in the left hemisphere this was also observed for the left insula and putamen, which were increased in OCD and reduced in ADHD. In addition both disorders have different frontal deficits. OCD patients have deficits in rostro-dorsal medial frontal regions that are important for top-down control of affect while ADHD patients had reduced activation in lateral inferior frontal cortex, a key area of attention and cognitive control. The findings fit into the notion of fronto-striatal dysregulation in OCD where basal ganglia are overactive and poorly controlled by medial frontal regions and a delayed fronto-striatal maturation in ADHD where both lateral frontal regions and the basal ganglia/insula are smaller, and presumably less developed in structure and in function in ADHD. (more…)
Author Interviews, CMAJ, Neurological Disorders, Pain Research / 07.06.2016

MedicalResearch.com Interview with: Dr Vincent Chung Assistant Professor, Jockey Club School of Public Health and Primary Care Associate Director (Education), Hong Kong Institute of Integrative Medicine Registered Chinese Medicine Practitioner The Chinese University of Hong Kong MedicalResearch.com: What is the background for this study? Response: Primary carpal tunnel syndrome (CTS) is one of the most common forms of peripheral entrapment neuropathy. It is a major cause of disability on the upper extremity incurring considerable limitation on daily activities among patients. Currently, there is no consensus on appropriate treatment for patients with chronic (≥6 months) mild to moderate symptoms [Archives of physical medicine and rehabilitation. 2014;95(12):2253-63]. Electroacupuncture is a common technique for managing pain and neuropathy in Chinese medicine. Current CTS treatment guidelines from the UK National Institute for Health and Care Excellence (NICE), American Academy of Orthopaedic Surgeons (AAOS) and the American College of Occupational and Environmental Medicine (ACOEM) made no specific recommendations for or against electroacupuncture. (more…)
Author Interviews, Epilepsy, Neurological Disorders, PLoS / 30.05.2016

MedicalResearch.com Interview with: Amanda Sierra, PhD Research Professor and Group Leader Ramón y Cajal Fellow Achucarro Basque Center for Neuroscience Laida Bidea Bizkaia Science and Technology ParkAmanda Sierra, PhD Research Professor and Group Leader Ramón y Cajal Fellow Achucarro Basque Center for Neuroscience Laida Bidea Bizkaia Science and Technology Park Zamudio, Bizkaia, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sierra: Microglia phagocytosis of apoptotic cells is at the core of the brain regenerative response to recover the homeostasis of the brain parenchyma after damage because it prevents the spillover of toxic intracellular contents and is actively anti-inflammatory. However, while neuronal death is widespread in neurodegenerative diseases (Alzheimer´s, Parkinson´s, multiple sclerosis) and well as in ischemic and traumatic brain injuries, we have a complete lack of knowledge of the efficiency of microglial phagocytosis in the diseased brain. In this paper we have discovered that microglia have a generalized response to apoptotic challenges: when confronted to a rise in the number of newborn cells, microglia display a combination of different strategies to boost their phagocytic output: increase the phagocytic capacity of each cell, recruit more cells to become phagocytic, or increase the total number of microglia (Abiega et al., PLoS Biol 2015). Thus, microglia have a very large potential for phagocytosis that could be summoned when needed. To our surprise, however, in pathological conditions such as epilepsy (mouse and human), microglial phagocytosis was blocked. We have made use of the adult neurogenic cascade, where newborn cells undergo apoptosis naturally and are engulfed by “unchallenged microglia” (Sierra et al. Cell Stem Cell 2010), to establish the baseline of microglial phagocytosis efficiency. Whereas in physiological conditions microglia phagocytose over 90% of the apoptotic cells and remove them in under 1.5h, soon after the seizures it only engulfed 10% of the apoptotic cells and took up to 6h to digest them. This is the first quantification of microglial phagocytosis efficiency in the diseased mouse and human brain.. The block in phagocytosis was a rather complex phenomenon related to an impaired recognition (reduction of phagocytosis receptors) as well as impaired motility and targeting (reduced basal motility). We have also shown that the impairment is mediated at least partially by altered ATP microgradients: ATP is not only a neuro- and gliotransmitter widely released during seizures but is also a well-known “find-me” signal released by apoptotic cells. Thus, during seizures microglia became “blinded” by the neuronal hyperactivity and could not find the apoptotic cells. In addition, we have shown that impairing phagocytosis releases the break on the inflammatory response. In fact, the impaired microglia were in a pro-inflammatory state and produced more cytokines such as tumor necrosis factor alfa (TNFa) or interleukin-1beta (IL-1b), which are well known neurotoxic and epileptogenic factors. (more…)
Author Interviews, Microbiome, Neurological Disorders / 22.05.2016

MedicalResearch.com Interview with: Susanne Asu Wolf PhD Max-Delbrueck-Center for Molecular Medicine Berlin, Germany MedicalResearch.com: What inspired you to research this link between Ly6Chi monocytes, antibiotics and neurogenesis? Dr. Wolf: As a neuroimmunologist I research the communication between the immune system and the brain. Amongst other research groups we found almost 10 years ago that T cells are needed to maintain brain homeostasis and plasticity, namely neurogenesis. Since only activated T cells enter the brain, we were looking for a mouse model, where immune cells are not activated. My former supervisor Polly Matzinger (NIH), a well-known immunologist, suggested to use germ free mice, born and raised in an isolator without any contact to a pathogen or any bacteria. I did a pilot experiment with the germ free mice, but wanted to get closer to possible applications in humans. Since humans are rarely born and raised in a sterile environment, I was looking for another model. By chance I met with the group of Bereswill and Heimesaat (Berlin, Charite) who provided me with a model, where due to prolonged treatment with an antibiotic cocktail, the microbiota are below detection level and the mice are also virtually germ free. They got me into contact with the second senior author of the paper Ildiko Dunay (University of Magdeburg). Her expertise is the function of Ly6Chi monocytes during infection with malaria or toxoplasmosis. Now we were ready to investigate the gut-immune-brain axis with the focus on neurogenesis and cognition. Meanwhile the impact of the microbiome on behavior was reported by several research groups using “sterile” germ free mice and I was also curious if we could see similar differences in our antibiotic treated mice. (more…)
Author Interviews, Multiple Sclerosis, PLoS, Vitamin D / 19.05.2016

MedicalResearch.com Interview with: Ms Emily Weiss PhD student Centre for Population Health Sciences The University of Edinburgh

MedicalResearch.com: 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…)
Author Interviews, Cancer Research, Colon Cancer, Immunotherapy, Leukemia, Multiple Sclerosis, Neurology / 13.05.2016

MedicalResearch.com Interview with: PD Dr. Mathias Buttmann Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic University of Wuerzburg Wuerzburg, Germany  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated  multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer. Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer. (more…)
Artificial Sweeteners, Author Interviews, Brain Injury, JAMA, Neurological Disorders, Ophthalmology / 12.05.2016

MedicalResearch.com Interview with: Dr. T. Dianne Langford PhD Associate Professor, Neuroscience and Neurovirology Lewis Katz School of Medicine Temple University MedicalResearch.com: What is the background for this study? Dr. Langford: The ocular-motor system has been shown to reflect neural damage, and one of ocular-motor functions, near point of convergence (NPC), was reported to worsen after a sport-related concussion (Mucha et al. Am J Sport Med). But the effects of subconcussive head impact, a milder form of head injury in the absence of outward symptoms remains unknown.  Prior to this study, we found that in a controlled soccer heading experimental paradigm decreased NPC function, and even 24h after the headings, NPC was not normalized back to baseline (Kawata et al. 2016 Int J Sport Med). To extend our findings from the human laboratory study, we launched longitudinal clinical studies in collaboration with the Temple football team, to see if repetitive exposure to subconcussive head impacts negatively affects NPC. (more…)
ALS, Alzheimer's - Dementia, Author Interviews, Nature / 07.05.2016

MedicalResearch.com Interview with: Ana Pereira, MD Instructor in Clinical Medicine Bruce McEwen's laboratory Rockefeller University  MedicalResearch.com: What is the background for this study? Dr. Pereira: The neurons most susceptible to dying in Alzheimer’s disease are the ones that use glutamate as a neurotransmitter (chemical messengers that enable neurotransmission). Glutamate is the major excitatory neurotransmitter in the brain and its regulation is critical for learning and memory. When glutamate is not located in the correct place and amount, it causes several deleterious effects to neurons that can ultimately lead to cell death. Importantly, the glutamate transporter EAAT2 is the dominant regulator of glutamate levels and it is highly depressed in Alzheimer’s disease. Furthermore, glutamatergic dysregulation is implicated in several pathological mechanisms in Alzheimer’s disease including the release and toxicities of the proteins implicated in Alzheimer’s disease: amyloid-beta (which form amyloid plaques) and tau (which form neurofibrillary tangles). Better regulation of glutamatergic neural circuits is critically important to effectively treat age-related cognitive decline and Alzheimer’s disease. (more…)
Author Interviews, Immunotherapy, JAMA, Multiple Sclerosis, UCSF / 02.05.2016

MedicalResearch.com Interview with: Jennifer Graves, MD, PhD, MAS Adult and Pediatric Multiple Sclerosis Centers UCSF MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Graves: Cessation of medications with effects on immune trafficking may be more likely to cause rebound inflammatory activity in autoimmune diseases such as multiple sclerosis.  We observed 5 strikingly severe relapses consistent with rebound events following cessation of fingolimod treatment and identified several similar cases in the literature.  At our center the rebound events occurred with an approximate 10% frequency. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Graves: Fingolimod cessation may be complicated by rebound phenomena in some patients, similar to what has been observed with natalizumab. Both of these medications have effects on immune cell trafficking, likely explaining the association with rebound events.  Careful consideration must be taken in stopping these medications. (more…)
Author Interviews, Epilepsy, NYU / 01.05.2016

MedicalResearch.com Interview with: Jacqueline French, MD Professor, Department of Neurology Director Translational Research& Clinical Trials Epilepsy NYU Langone Medical Center  MedicalResearch.com: What is the background for this study? Dr. French:  Tuberous sclerosis complex (TSC) is a disease associated with abnormal cell growth, caused by dysfunction of the TSC1 or TSC2 genes and dysruption of the MTOR pathway, which leads to cortical malformations, neuronal hyperexcitability, and seizures. Seizures in patients with TSC often start within the first year of life, and tend not to respond to traditional treatments. Everolimus is a marketed drug that has been used to treat other manifestations of TSC (including giant cell tumors of the brain, renal angiomyolipomas, and angiofibromas of the skin). This study was a placebo-controlled add-on study of everolimus for the treatment of refractory seizures in children and adults with epilepsy.Following an 8-week baseline phase, patients aged 2-65 years (stratified by age) with TSC and refractory seizures on 1-3 antiepileptic drugs were randomized to EVE LT or HT Cmin target ranges or placebo, and treated in an 18 week Core Phase (6-wk titration + 12-wk maintenance). Primary endpoints were change from baseline in average weekly frequency of TSC-seizures (seizures not previously shown to be generalized in onset by EEG), expressed as response rate (≥50% reduction [RR]), and percentage reduction. MedicalResearch.com: What are the main findings? Dr. French:  Overall, 366 patients were randomized to EVE LT (n=117), HT (n=130), or placebo (n=119). The median percentage reduction in TSC-seizures was significantly greater with EVE LT (29.3%, P=0.003) and HT (39.6%, P<0.001) vs placebo (14.9%). RR was also significantly greater with EVE LT (28.2%, P=0.008) and HT (40%, P<0.001) vs placebo (15.1%). The most frequent ≥10% all grade adverse events (AEs) reported with EVE LT/HT vs placebo included stomatitis (28.2%/30.8% vs 3.4%), diarrhea (17.1%/21.5% vs 5%), mouth ulceration (23.9%/21.5% vs 4.2%), nasopharyngitis (13.7%/16.2% vs 16%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), aphthous ulcer (4.3%/14.6% vs 1.7%), and pyrexia (19.7%/13.8% vs 5%). Discontinuations due to AEs (5.1%/3.1% vs 1.7%) were low. (more…)
Author Interviews, Multiple Sclerosis, Neurology, NYU / 21.04.2016

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Neurological Disorders, Psychological Science / 19.04.2016

MedicalResearch.com Interview with: Ezequiel Morsella, Ph.D. Associate Professor of Neuroscience Department of Psychology San Francisco State University Assistant Adjunct Professor Department of Neurology University of California, San Francisco Boardmember, Scientific Advisory Board Institute of Cognitive Neurology (INECO), Buenos Aires MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Morsella: The study is based on Passive Frame Theory, which I discuss below in brief, and on ironic processing, in which one is more likely to think about something (e.g., white bears) when instructed to not think about that thing.  Based on this research, the Reflexive Imagery Task (RIT) reveals that, following the activation of certain "action sets" (i.e., dispositions to act one way or another), conscious thoughts can arise involuntarily and systematically when one is presented with certain stimuli.  In the most basic version of the RIT, subjects are presented with visual objects and instructed to not think of the names of the objects, which is challenging.  In the new study, we show that the effect arises not only for automatic processes (e.g., forms of cued-memory retrieval) but also for processes involving more, in a sense, moving parts (e.g., symbol manipulation, in which symbols are mentally manipulated).  In the study, subjects were first trained to perform a word-manipulation task similar to the game of Pig Latin (e.g., “CAR” becomes “AR-CAY”). This task involves complex symbol manipulations.  After training, though participants were instructed to no longer transform stimulus words in this way, the RIT effect still arose on roughly 40% of the trials. The present experiment provides additional evidence for Passive Frame Theory, a new, comprehensive and internally coherent framework that illuminates the role of conscious processing in the brain. Click here for more information about Passive Frame Theory: https://www.psychologytoday.com/blog/consciousness-and-the-brain/201604/passive-frame-theory-new-synthesis Although consciousness is not "epiphenomenal" (meaning that it serves no function) or omnipresent (e.g., as in panpsychism, which states that consciousness is a property of all matter), in Passive Frame Theory, the role of consciousness is much more passive and less teleological (i.e., less purposeful) than that of other theoretical accounts. The framework reveals that consciousness has few moving parts and no memory, no reasoning, or symbol manipulation, which is relevant to the present study. Consciousness does the same thing, over and over, for various processes, making it seem that it does more than it does.  Hence, consciousness, over time, seems to be more flexible than it actually is. (more…)
Author Interviews, Nature, Neurological Disorders / 19.04.2016

MedicalResearch.com Interview with: Phillip G. Popovich, Ph.D. Professor, Neuroscience Director, Center for Brain and Spinal Cord Repair Ray W. Poppleton Research Designated Chair Department of Neuroscience Wexner Medical Center at The Ohio State University Columbus, Ohio  43210 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Popovich:  People that suffer a spinal cord injury (SCI) at a high spinal level (e.g., cervical SCI), are at increased risk for developing autonomic dysreflexia (AD), a potentially life-threatening condition of sudden onset high blood pressure. In people and animals with SCI, reflexes that are activated by routine stimuli including filling of the bladder or bowel often trigger AD. We recently found that these same reflexes also suppresses the immune system (see Zhang et al., 2013; PMID 23926252) Since people with high level  spinal cord injury also are at increased risk for developing infections (e.g., pneumonia), we set out to understand how SCI changes the autonomic circuitry in the spinal cord that controls immune function. We found that after a period of one month, the number of connections between spinal cord interneurons and autonomic neurons that directly control immune function increases dramatically. Also, this newly formed circuitry is “hyperactive” and discharge of neurons in this circuit causes hormones to be released into the blood and immune organs that overstimulate immune cells, causing them to die. Fortunately, we were able to show that the hyperactive spinal cord circuitry can be silenced. We used a novel technique known as “chemogenetics” to silence excitatory interneurons in the aberrant circuit. When the circuitry was silenced, immune cells were protected in spinal cord injury mice. (more…)
Author Interviews, Brain Injury, Neurological Disorders / 13.04.2016

MedicalResearch.com Interview with: Thomas A. Buckley Ed.D Assistant Professor Kinesiology & Applied Physiology 144 Human Performance Lab College of Health Sciences University of Delaware MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Buckley: The most recent international consensus statement recommends 24 - 48 hours of cognitive and physical rest in the immediate aftermath of a concussion; however, our clinical experience was that patients who were "shut down" for a few days did worse than patients who were allowed to be out and about as tolerated by symptoms.  This was a retrospective study (chart review) comparing symptom reporting among patients who were shut down for 24 hours and those who were not. The main finding of the study was the addition of a day of cognitive and physical rest (i.e., 'shut down") did not improve symptom recovery recovery.  In fact, we were surprised to see that the non-rest group was symptom free 1.3 days sooner than the rest group and this was statistically significant. (more…)
Author Interviews, Multiple Sclerosis, PNAS / 12.04.2016

MedicalResearch.com Interview with: 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). (more…)
Author Interviews, Microbiome, Multiple Sclerosis / 05.04.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Dermatology, JAMA, Parkinson's / 21.03.2016

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Egeberg: Rosacea skin shows an up-regulation of various cytokines (small proteins that are important in cell signalling), and displays increased activation and expression of matrix metalloproteinases (MMPs). Both rosacea and Parkinson’s disease have been associated with small intestinal bacterial overgrowth and Helicobacter pylori infection, and MMPs. MMPs are enzymes that are involved in tissue remodeling, organ development, and regulation of inflammatory processes. Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. Importantly, MMPs have also been implicated in the pathogenesis of Parkinson’s disease and other neurodegenerative disorders, and MMPs contribute to loss of dopamine producing brain cells. Rosacea is often characterized by flare-ups and remissions and typically presents as a redness on the cheeks, nose, chin or forehead. In our study, we found a significantly (approximately two-fold) increased risk of developing Parkinson's disease, a chronic and progressive movement disorder, among patients with rosacea. Also, we found that treatment with tetracycline, an oral antibiotic, was associated with a slightly decreased risk of Parkinson's disease. (more…)
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. (more…)
Author Interviews, Lancet, Neurological Disorders, Pain Research / 07.03.2016

MedicalResearch.com Interview with: Nadine Attal, MD PhD Professeur associée de l'UVSQ INSERM U 987 et CETD CHU Ambroise Paré 92100 Boulogne-Billancourt MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Attal: The background for this study is based on the findings of experimental studies in animals and healthy subjects indicating that botulinum toxin type A  (BTX-A) may have analgesic activity independent of its effect on muscle tone. BTX-A has been reported to have analgesic effects against peripheral neuropathic pain in prior trials, but the quality of the evidence was generally low, as it was derived mostly from small pilot studies and no study has evaluated the relevance of repeated administrations for the treatment of NP. Furthermore, the clinical profiles of the patients responding to BTX-A have not been fully characterized. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Attal: They should take away that two repeated subcutaneous administrations of botulinum toxin type A are effective in peripheral  neuropathic pain but mostly in patients with allodynia and/or limited thermal deficits. BTX-A also appears to be particularly effective on paroxysmal pain (ie electric shock like pain). Finally, the efficacy of a second administration of BTX-A is enhanced over the first injection. (more…)
Author Interviews, BMJ, Coffee, Karolinski Institute, Multiple Sclerosis / 04.03.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Neurological Disorders, Stroke / 29.02.2016

MedicalResearch.com Interview with: Georgios Tsivgoulis , M.D., Ph.D., MSc, FESO Assistant Professor of Neurology University of Athens, Athens, Greece Visiting Associate Professor of Neurology Director of Stroke Research Department of Neurology University of Tennessee Health Science Center Medical Research: What is the background for this study? What are the main findings? Dr. Tsivgoulis: Literature data suggest that taking statins before an acute ischemic stroke may improve early outcomes including early neurological deterioration, mortality and disability in patients with acute ischemic stroke. However,the potential beneficial effect of statin pretreatment has never been investigated in acute ischemic stroke due to large artery atherosclerosis. The research question in this specific subgroup of ischemic stroke patients is of great importance, as large-artery atherosclerotic stroke carries the highest risk of early recurrent stroke in comparison to other acute ischemic stroke subtypes. Using prospectively collected data from over 516 consecutive patients with acute large-artery atherosclerotic stroke from seven tertiary-care stroke centers during a three-year period we found that statin pretreatment in patients with acute large-artery atherosclerotic stroke is associated with better early outcomes in terms of neurological improvement, disability, survival and stroke recurrence. (more…)
Author Interviews, Neurological Disorders, NYU / 26.02.2016

MedicalResearch.com Interview with: Michael A. Long, PhD New York University School of Medicine Assistant Professor New York Stem Cell Foundation Robertson Neuroscience Investigator Medical Research: What is the background for this study? Response: Speech is, of course, central to our everyday lives, and it is perhaps the most thoroughly studied human behavior.  That said, many aspects of how our brain produces speech are still poorly understood. Human brains are extremely complex, and many of the tools that are available to understand the function of the brain are quite limited.  Although we have a good idea of the brain regions involved in producing speech, our understanding of the roles that each area plays to enable us to produce words is much less clear. Medical Research: How did you become interested in this problem?  Response: I am a basic researcher focusing on the mechanisms that enable the brain to produce complex behaviors.  We primarily study the songbird brain, which contains several clearly defined areas that are dedicated to producing the song.  Through careful study, many research groups have discovered how these areas are working together to produce the song.  I realized that this kind of perspective may be useful to further our understanding of human speech production. Medical Research: How did you translate the findings from the songbird brain to the human brain? Response: Many years ago, when I was a postdoc with Michalel Fee at MIT, I used a small head-mounted cooling device to selectively lower the temperature of specific brain regions in the songbird by a few degrees.  To our surprise and delight, the cooling of a specific brain area – called HVC – resulted in a slowing of the tempo of that song.  From this finding, we realized that HVC was a key timing center for singing, and by cooling that ‘clock’, the song that was produced happened more slowly. When I established my own lab at NYU, I reached out Dr. Matthew Howard’s Neurosurgery group at the University of Iowa because of his impressive history of making fundamental discoveries about human brain function.  There I met Dr. Jeremy Greenlee, and we discussed using a cooling approach for understanding human speech.  Since 2011, we worked with 22 patients that were undergoing neurosurgery for either epilepsy or tumor removal.  Patients were asked to recite simple lists of words, like the days of the week, while a device with a footprint about the size of a quarter would cool different places along the surface of the brain.  (more…)
Author Interviews, Diabetes, Neurological Disorders, Yale / 26.02.2016

MedicalResearch.com Interview with: Sabrina Diano, Ph.D. Professor, Depts. Ob/Gyn, Neuroscience and Comparative Medicine Associate Chair for Faculty Development Dept Ob/Gyn and Reproductive Sciences Program in Cell Signaling and Neurobiology of Metabolism Yale University School of Medicine and Graduate School  Medical Research: What is the background for this study? What are the main findings? Dr. Diano: We have been studying the intracellular mechanisms that regulate glucose sensing by the brain. We found that in a specific area of the brain (called ventromedial nucleus of the hypothalamus) a small group of neurons (the brain cells) are able to sense increased glucose levels in the blood via their mitochondria, the energy powerhouse of the cells. This mitochondrial change enables these neurons to get activated, which in turn, results in a reduction of  glucose levels in the blood due to an increased muscles glucose utilization. (more…)
Author Interviews, Compliance, Neurological Disorders, Stroke / 23.02.2016

MedicalResearch.com Interview with: Dr-William-Patrick-Neil William P. Neil, MD Vascular Neurologist SCPMG Regional Stroke Champion Neurology    Medical Research: What is the background for this study? Dr. Neil: Stroke survivors are less likely to have a recurrent stroke, or other complications if they take their medications as prescribed by their doctor. Mail order pharmacies are increasingly being used to deliver medications for a variety of diseases, and their use is associated with better medication adherence.  We wanted to see whether stroke patients who use mail-order pharmacies were more likely to have good medication adherence than those who used  local pharmacies. Medical Research: What are the main findings? Dr. Neil: We looked through a large electronic medical database in California, and found a total of 48,746 people discharged from the hospital with a stroke, and who also filled either a cholesterol medication or an anticoagulant (blood thinner). Of these, 136,722 refills were from a local pharmacy and 68,363 were by mail. Overall, patients were adherent to the medications 46.5% of the time if they picked up the medication from the pharmacy and 74% of the time if they had prescriptions mailed to them. (more…)