Author Interviews, Neurological Disorders, Neurology, Personalized Medicine, Radiology, Surgical Research / 13.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43125" align="alignleft" width="139"]Yasser Iturria-Medina, PhD Primary Investigator, Ludmer Centre for Neuroinformatics & Mental Health Assistant Professor, Department of Neurology and Neurosurgery Faculty of Medicine McGill University Dr. turria-Medina[/caption] Yasser Iturria-Medina, PhD Primary Investigator, Ludmer Centre for Neuroinformatics & Mental Health Assistant Professor, Department of Neurology and Neurosurgery Faculty of Medicine McGill University MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are millions of patients following therapeutic interventions that will not benefit them. In this study, we aimed to illustrate that it is possible to identify the most beneficial intervention for each patient, in correspondence with the principles of the personalized medicine (PM). Our results show that using multimodal imaging and computational models it is possible to predict individualized therapeutic needs. The predictions are in correspondence with the individual molecular properties, which validate our findings and the used computational techniques. The results highly also the imprecision of the traditional clinical evaluations and categories for understanding the individual therapeutic needs, evidencing the positive impact that would have to use multimodal data and data-driven techniques in the clinic, in addition to the medical doctor's criterion/evaluations.  
Author Interviews, Kidney Disease, Neurological Disorders, Pain Research, UCSF / 06.06.2018

MedicalResearch.com Interview with: [caption id="attachment_42216" align="alignleft" width="150"]Dr. Julie H. Ishida MD Department of Medicine, Division of Nephrology University of California, San Francisco and San Francisco Veterans Affairs Medical Center Dr. Ishida[/caption] Dr. Julie H. Ishida MD Department of Medicine, Division of Nephrology University of California, San Francisco and San Francisco Veterans Affairs Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gabapentin and pregabalin are used for the management of symptoms such as neuropathic pain, itching, and restless leg syndrome in patients receiving hemodialysis. However, hemodialysis patients may be particularly vulnerable to adverse events related to these agents, which are cleared by the kidney, but there is limited data evaluating their risk in this population. Gabapentin and pregabalin use were associated with risk for altered mental status, fall, and fracture, and in some cases, even at doses that would be considered safe for use in this population. 
Author Interviews, CDC, JAMA, Neurological Disorders, Zika / 31.05.2018

MedicalResearch.com Interview with: [caption id="attachment_41893" align="alignleft" width="125"]Dr. Emilio Dirlikov, PhD Office of Epidemiology and Research, Puerto Rico Department of Health Epidemic Intelligence Service Division of Scientific Education and Professional Development CDC Dr. Dirlikov[/caption] Dr. Emilio Dirlikov, PhD Office of Epidemiology and Research, Puerto Rico Department of Health Epidemic Intelligence Service Division of Scientific Education and Professional Development CDC MedicalResearch.com: What is the background for this study? What are the main findings? Response: After reporting local Zika transmission in December 2015, the Puerto Rico Department of Health (PRDH), US Centers for Disease Control and Prevention (CDC), and University of Puerto Rico began identifying cases of Guillain-Barré syndrome (GBS), testing specimens, and conducting follow-up telephone interviews after patients left the hospital. Through these efforts, we were able to characterize acute clinical features and long-term disability of GBS associated with Zika infection by analyzing data from GBS patients with and without evidence of Zika infection. This investigation increases scientific and medical understanding of Guillain-Barré syndrome following Zika infection, provides insight into the disease processes involved in GBS following Zika infection, and adds to growing evidence of a causal association between Zika and GBS. 
Author Interviews, Epilepsy, Neurological Disorders, NYU/NYMC, Pharmaceutical Companies / 17.05.2018

MedicalResearch.com Interview with: https://www.gwpharm.com/epilepsy-patients-caregivers/patientsAnup Patel, M.D. Section Chief of Neurology Interim Division Chief of Neurology Nationwide Children’s Hospital MedicalResearch.com: What is the background for this study? Response: The study evaluated kids and adults with an epilepsy syndrome (Lennox Gastaut Syndrome – LGS) that is often difficult to treat and does not respond well to current medical treatment.  The study was a double blind randomized control trial evaluating how well a plant based, liquid solution, cannabidiol (CBD) product made by Greenwich Biosciences called Epidiolex helped to treat drop seizures (the most common seizure type in LGS) and how safe it was compared to placebo.  Two doses (10 mg/kg/day and 20 mg/kg/day) were evaluated compared to placebo.
Author Interviews, Emory, Hematology, JAMA, Neurological Disorders, Stroke / 23.04.2018

MedicalResearch.com Interview with : [caption id="attachment_41371" align="alignleft" width="200"]Dr. Hyacinth I Hyacinth MD Aflac Cancer and Blood Disorder Center, Emory Children’s Center, Department of Pediatrics, Emory University School of Medicine Atlanta, GA 30322 Dr. Hyacinth[/caption] Dr. Hyacinth I Hyacinth MD Aflac Cancer and Blood Disorder Center, Emory Children’s Center, Department of Pediatrics, Emory University School of Medicine Atlanta, GA 30322 MedicalResearch.com: What is the background for this study? This study was conducted against the backdrop of a significantly higher risk for stroke among African Americans compared to non-Hispanic Whites, despite adjusting for traditional risk factors. Also, sickle cell disease is a well-known genetic risk factor for stroke and recent studies show that sickle cell trait is a risk factor for chronic kidney disease, venous thromboembolism and pulmonary embolism, all of which are potential risk factors for stroke.
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Epilepsy / 12.04.2018

MedicalResearch.com Interview with: Britta Haenisch, PhD Pharmacoepidemiology in Neurodegenerative Disorders German Center for Neurodegenerative Diseases, DZNE  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Antiepileptic drugs (AEDs) have been shown to affect cognition by suppressing neuronal excitability and increasing inhibitory neurotransmission. Previous studies suggested that AEDs may be associated with cognitive adverse effects. Therefore, we evaluated the association between AED use and incident dementia and Alzheimer’s disease (AD). We utilized large longitudinal datasets from Finnish health registers and from German health insurance data. The case-control analyses was adjusted for several potential confounders like comorbidities and polypharmacy. The inclusion of a lag time between . Antiepileptic drugs use and dementia diagnosis allowed minimization of protopathic bias. Our study provides an association between regular prescription of  antiepileptic drugs with known cognitive adverse effects and the occurrence of dementia and AD in patients aged 65 years and older. 
Author Interviews, Epilepsy, JAMA / 10.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41045" align="alignleft" width="183"]Dr Hayley Gorton PhD MPharm MRPharmS FHEA Research Associate Centre for Pharmacoepidemiology and Drug Safety Research Division of Pharmacy & Optometry| Faculty of Biology, Medicine & Health University of Manchester Dr. Gorton[/caption] Dr Hayley Gorton PhD MPharm MRPharmS FHEA Research Associate Centre for Pharmacoepidemiology and Drug Safety Research Division of Pharmacy & Optometry| Faculty of Biology, Medicine & Health University of Manchester MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is already known that people with epilepsy are at a higher risk of death than those without epilepsy but we didn’t know much about the risks of different types of death. Unnatural death (mainly accident and suicide) accounts for a very small number of all deaths but, compared to people without epilepsy, people with epilepsy are three times more likely to die by accident and twice as likely to die by suicide. Within these broad categories, persons with epilepsy are five times more likely to die specifically by accidental poisoning with medication, and three times more likely to die by intentionally poisoning themselves with medication. Opioid painkillers and medicines for mental illness were the ones most commonly used in poisoning deaths among people with epilepsy and those without epilepsy. Antiepileptic drugs were taken relatively infrequently-they were involved in about 10% of poisoning deaths in people with epilepsy. 
ALS, Alzheimer's - Dementia, Author Interviews, JAMA / 09.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41048" align="alignleft" width="137"]Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis Dr. Karch[/caption] Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nearly half of all patients with amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disorder, develop cognitive problems that affect memory and thinking. Why a disease that primarily affects movement also disrupts thinking has been unclear. Our findings suggest that genetic connections between the two disorders may explain why they share some of the same features and suggest that some drugs developed to treat ALS also may work against frontotemporal dementia and vice versa. We used a statistical method in almost 125,000 individuals with ALS, frontotemporal dementia (FTD), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease and Parkinson’s disease to determine whether there are common genetic variants that increase risk for multiple neurodegenerative diseases. We found that common variants near the MAPT gene, which makes the tau protein, increases risk for ALS. MAPT has previously had been associated with diseases including frontotemporal dementia and Alzheimer’s disease. But the gene hadn’t been linked to ALS. We also identified variations in a second gene, BNIP1, which normally plays an important role in protecting against cell death, increased the risk of both ALS and frontotemporal dementia. ImportantlyBNIP1 mRNA levels were altered in people who had ALS and in patients with frontotemporal dementia, suggesting the BNIP1 may be a potential therapeutic target for both disorders.
Alzheimer's - Dementia, Author Interviews, JAMA, Parkinson's / 27.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40768" align="alignleft" width="147"]Benjamin Dawson, B.Sc.  MD Candidate 2020 Benjamin Dawson[/caption] Benjamin Dawson, B.Sc. MD Candidate 2020 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dementia in Parkinson’s Disease is one of its most feared complications, and may happen eventually to most patients if they reached advanced age. Identifying those at especially high risk of dementia has important potential implications - it would facilitate clinical counselling, it has treatment implications (e.g. knowing a person is likely to get dementia in the near future would probably steer you away from certain medications and towards others).  Most critically, it can help select patients for trials to prevent dementia. While several factors that show high risk for dementia in Parkinson’s disease have previously been described, these have yet to shape patient-care, either because they are not very strong predictors, or they are not user-friendly.  So, we designed a very simple clinical screening tool, called the Montreal Parkinson’s Risk of Dementia Scale (MoPaRDS).  It took predictors of dementia that were established from large-scale studies and boiled them down into a simple 8-point scale that uses information that you can get in a simple office visit.  The 8 predictors were being over 70, being male, having a blood pressure drop with standing, showing early mild cognitive changes, having a symmetric bilateral disease (that is, one side not clearly worse than the other), experiencing falls or freezing, having experienced hallucinations, and having symptoms of REM sleep behavior disorder ('acting out' the dreams at night). When we tested the scale in a combined cohort of 607 patients with Parkinson’s (of whom 70 developed dementia over mean follow-up of 4.4-years) a positive MoPaRDS screen (≥4 out of 8 items) identified 14-fold increased risk of dementia compared to a negative screen. We recommend dividing the scale into three categories; low-, intermediate- and high-risk. Those in the highest score group (MoPaRDS, 6-8) had a 14.9% risk of developing dementia each year, while those with the lowest scores (MoPaRDS, 0-3) had only 0.6% annual risk.  So, these simple measures can be pretty powerful predictors of dementia.
Author Interviews, Lancet, Neurological Disorders, Neurology / 23.03.2018

MedicalResearch.com Interview with: David Birnkrant, MD Professor of Pediatrics, Case Western Reserve University School of Medicine Director of Pediatric Pulmonology & Student Education, MetroHealth Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study updates guidance on all aspects of the multi-disciplinary care of patients with Duchenne muscular dystrophy (DMD). The project was funded by the CDC’s National Center on Birth Defects and Developmental Disabilities and the results were recently published as three articles in The Lancet Neurology. The project was guided by a 25-member steering committee. Eleven expert committees worked over a period of three years to develop guidelines based on the RAND/UCLA appropriateness method, in which assessments and interventions were evaluated for appropriateness and necessity. The recommendations update those originally published in 2010. Duchenne muscular dystrophy is transmitted by X-linked recessive inheritance and thus affects primarily boys and men. Patients affected by DMD do not produce functional dystrophin protein, resulting in progressive weakness of skeletal, respiratory, and heart muscles, causing a shortened life span. Teens and young men may require surgery for curvature of the spine, a ventilator device to assist breathing, and a feeding tube to help ensure adequate nutrition. The approach of the various subspecialties involved in DMD management has evolved, with more anticipatory assessment and therapy, identifying and addressing predictable medical complications as early as possible for optimal patient outcomes. With this kind of multi-disciplinary care, people with DMD now live into their 30s and beyond. Along with the emergence of new genetic and molecular therapies, the recognition that people with DMD are living longer was one of the main motivations behind the need for these updated care considerations. Patients with DMD, their families and their advocacy organizations are driving a new emphasis on optimizing quality of life, not just prolongation of survival. Thus, there was a need to address issues related to transitions of care from childhood to adulthood, coordination of care across subspecialties, and other topics related to education, vocation, independence, personal relationships, emotional health, and intimacy. The updated care considerations thus include eleven topic areas, eight of which were part of the 2010 guidelines. These are: (1) diagnosis, (2) neuromuscular management, (3) rehabilitation management, (4) gastrointestinal and nutritional management, (5) respiratory management, (6) cardiac management, (7) orthopedic and surgical management, and (8) psychosocial management. Three topics are new: (9) primary care and emergency management, (10) endocrine management (including growth, puberty, adrenal insufficiency, and bone health), and (11) transitions of care across the lifespan.
Author Interviews, Parkinson's / 11.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40490" align="alignleft" width="138"]Prof. Jeffrey Hausdorff PhD Director of the Center for the Study of Movement, Cognition and Mobility Full Professor in the Sackler School of Medicine and Sagol School of Neuroscience Tel Aviv Medical Center Prof. Hausforff[/caption] Prof. Jeffrey Hausdorff PhD Director of the Center for the Study of Movement, Cognition and Mobility Full Professor in the Sackler School of Medicine and Sagol School of Neuroscience Tel Aviv Medical Center MedicalResearch.com: What is the background for this study?  Response: Many people with Parkinson’s disease suffer from a disturbing symptom referred to as “freezing of gait”. When freezing occurs, the person’s feet inexplicably become stuck to the floor and he or she is unable to move forward, despite efforts to walk. Initially, the problem can last just a few seconds and occur very infrequently. As the problem progresses, however, freezing can last many seconds, occurring frequently throughout the day. This can lead to a very frustrating situation that may also be dangerous. People with freezing of gait have an increased risk of falls and reduced health-related quality of life. The behavioral manifestation of freezing of gait is a problem with walking, i.e., it is a “motor” symptom. However, there is also evidence that deficits in specific aspects of cognitive function (i.e., executive function) may also contribute to freezing of gait. The goals of the present work were to use non-invasive brain stimulation to better understand if these cognitive deficits are indeed in the causal chain and if non-invasive brain stimulation that simultaneously targets both motor and cognitive brain areas that are believed to involved with freezing have a better impact on freezing and related symptoms than stimulation that targets only motor brain areas or sham stimulation.
Author Interviews, Multiple Sclerosis, Ophthalmology, Pharmaceutical Companies / 08.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40544" align="alignleft" width="159"]Sarah A. Morrow MD, MS, FRCPC Associate Professor of Neurology Department of Clinical Neurological Sciences University of Western Ontario (Western) Dr. Morrow[/caption] Sarah A. Morrow MD, MS, FRCPC Associate Professor of Neurology Department of Clinical Neurological Sciences University of Western Ontario (Western) MedicalResearch.com: What is the background for this study? Response: Acute demyelinating optic neuritis, which presents with loss of vision and painful eye movements, is common in multiple sclerosis (MS) occurring 50% of persons with MS. High dose (≥ 1g) corticosteroids administered through an IV became the standard of practice after the landmark Optic Neuritis Treatment Trial as IV administration. However, in that study the IV dose of corticosteroids was much higher (1 gram daily) than the oral dose (1 mg/kg). Thus, it is not clear if IV administration is still better if equivalent doses are used orally. Oral administration is much more convenient for patients and less expensive, and previous studies showed that it is preferred by patients. In this study, we asked the following question: are high dose (≥ 1000mg) IV corticosteroids superior to equivalent doses of oral corticosteroids for the acute treatment of optic neuritis? We randomly assigned fifty-five cases of acute optic neuritis to 1000mg IV methylprednisolone or 1250mg oral prednisone daily for three days and compared recovery of their vision over the next 6 months. 
Author Interviews, Biomarkers, Neurological Disorders, University Texas, Zika / 07.03.2018

MedicalResearch.com Interview with: [caption id="attachment_40401" align="alignleft" width="177"]Slobodan Paessler, D.V.M., Ph.D. Associate Professor, Department of Pathology; Director, Galveston National Laboratory Preclinical Studies Core;  Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity; Member, Center for Biodefense & Emerging Infectious Diseases University of Texas Medical Branch  Galveston, TX Dr. Paessler[/caption] Slobodan Paessler, D.V.M., Ph.D. Professor, Department of Pathology; Director, Galveston National Laboratory Preclinical Studies Core; Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity; Member, Center for Biodefense & Emerging Infectious Diseases University of Texas Medical Branch Galveston, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: Zika virus infection is associated with various developmental issues for human embryos such as reduced head growth, reduced brain tissue growth, and damage to brain or eyes. We wanted to better understand if some of these birth defects are caused directly by the Zika virus or maybe by the host response to infection. In our study we demonstrate that the Zika virus infection induces autoimmune response against the C1q protein. This protein is a very important immune protein as well as one of the essential proteins for healthy brain development. Attacking the C1q protein upon exposure with the Zika virus could contribute to the development of autoimmune disorders and birth defects. 
ALS, Author Interviews, Neurological Disorders, Technology / 26.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39652" align="alignleft" width="240"]Matthew McKee/BrainGate Collaboration New technique enables rapid calibration of the BrainGate brain-computer interface.[/caption] David Brandman, MD, PhD Postdoctoral research associate (neuroengineering), Brown University Senior neurosurgical resident Dalhousie University BrainGate Website MedicalResearch.com: What is the background for this study? Response: People with cervical spinal cord injuries, ALS, or brainstem stroke, may lose some or all of their ability to use their arms or hands. In some cases, they may even lose the ability to speak. One approach to restoring neurologic function is by using a brain computer interface (BCI). BCIs record information from the brain, and then translate the recorded brain signals into commands used to control external devices. Our research group and others have shown that intracortical BCIs can provide people with tetraplegia the ability to communicate via a typing interface, to control a robotic limb for self-feeding, and to move their own muscles using functional electrical stimulation. Use of a BCI generally requires the oversight of a trained technician, both for system setup and calibration, before users can begin using the system independently. An open question with intracortical BCIs is how long it takes people to get up and running before they can communicate independently with 2 dimensional cursor control. The goal of this study was to systematically examine this question in three people with paralysis. As part of the ongoing BrainGate2 clinical trial, each study participant (T5, T8, and T10) had tiny (4x4 mm) arrays of electrodes implanted into a part of their brain that coordinates arm control. Each participant used motor imagery – that is, attempted or imagined moving their body – to control a computer cursor in real time.
Author Interviews, Genetic Research, JAMA, Neurology, Parkinson's / 25.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39579" align="alignleft" width="200"]Rachel Saunders-Pullman, MD, MPH Associate Professor of Neurology Icahn School of Medicine at Mount Sinai Chief, Movement Disorders, Mount Sinai Beth Israel Co-Director Clinical/Translational Research and Research Mentoring Movement Disorders, Department of Neurology, Mount Sinai Beth Israel New York, NY 10003 Dr. Saunders-Pullman[/caption] Rachel Saunders-Pullman, MD, MPH Associate Professor of Neurology Icahn School of Medicine at Mount Sinai Chief, Movement Disorders, Mount Sinai Beth Israel Co-Director Clinical/Translational Research and Research Mentoring Movement Disorders, Department of Neurology, Mount Sinai Beth Israel New York, NY 10003 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: There is a diversity in causes of Parkinson’s Disease (PD), and this may lead to heterogeneity in drug response. While LRRK2 PD due to G2019S mutations may fully mimic idiopathic PD (IPD), cross-sectional study suggests that the course may be slightly milder than IPD. Further, the pathology is heterogeneous with a minority not demonstrating Lewy bodies, and this may also correspond to less severe non-motor features. To better understand the course of PD associated with the G2019S LRRK2 mutation (the most common LRRK2 mutation), we evaluated motor and cognitive progression in individuals enrolled in the LRRK2 Ashkenazi Jewish Consortium. Subjects were recruited from a Center in Tel Aviv, Israel, Sourasky Medical Center, and from two centers in New York, Columbia University and Mount Sinai Beth Israel. 144 participants were LRRK2 mutation carriers and 401 were not. We utilized all study visits, and constructed linear mixed-effects models to estimate the association between harboring the LRRK2 mutation and rate of change of both motor features- as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS), and cognition, as measured by the Montreal Cognitive Assessment Scale (MoCA). Models adjusted for sex, site, age, disease duration and (for the motor models) cognitive score. We found a small but significant difference in rate of progression, with LRRK2 PD progressing at 0.69 points/year, and IPD at 1.06 points/year. While the cognitive decline was also less in the LRRK2 PD (-0.10 vs. -0.19 in the IPD, this difference was not statistically different (p=0.08).
Author Interviews, JAMA, Multiple Sclerosis, Radiology / 04.01.2018

MedicalResearch.com Interview with: Netta Levin MD PhD fMRI lab Neurology Department Hadassah Hebrew University Medical Center Jerusalem  MedicalResearch.com: What is the background for this study? Response: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, manifesting with episodes of local inflammatory processes, called relapses. The most useful surrogate laboratory test for MS is magnetic resonance imaging (MRI), in which dissemination of demyelinating lesions in space and time are the hallmark of the disease. However, there is a discrepancy between the lesion load - the number, size, and location of the lesions - and the clinical state of the patients, reflected in their disability. This discrepancy is known as the “clinico-radiological paradox” and suggests that something other than the well-known mechanisms of demyelination, remyelination, and axonal loss may tip the scale of recovery from an acute episode. Global effects of the local damage and compensatory mechanisms were suggested as an explanation to this paradox. In this study, we compared the visual system of patients with clinically isolated syndrome optic neuritis (ON) to patients with clinically isolated episodes in other functional systems, exploring changes, both anatomical and functional, caused to the system following the demyelinating episode. Optic neuritis was deemed a good in vivo model for studying the pathophysiology of tissue damage and repair in MS due to its characteristic clinical manifestation and to the visual pathways’ amenability to investigation using various techniques. To assess anatomical wiring ,i.e the white matter fibers themselves , we used diffusion tensor imaging (DTI). To assess functional networking as reflected by signal synchronization between distinct brain regions, we used resting state fMRI.
Author Interviews, Parkinson's / 28.12.2017

MedicalResearch.com Interview with: Dr. Frances M. Weaver PhD Hines VA Hospital Center of Innovation for Complex Chronic Healthcare Hines, IL 60141 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Research has shown that deep brain stimulation (DBS) for Parkinson’s disease (PD) improves motor function and this improvement is sustained. There is also improvement in quality of life after DBS. However, it is not known whether DBS also effects survival. A few studies that have examined survival have had mixed results. In the current study we compared survival for a large cohort of persons with Parkinson’s disease who underwent DBS to a match group of persons with PD who were managed medically. We found a modest improvement in survival for persons with Parkinson’s disease who underwent DBS compared to individuals who did not.
Author Interviews, Parkinson's, Pharmacology / 14.12.2017

MedicalResearch.com Interview with: [caption id="attachment_38919" align="alignleft" width="200"]Dr. Youcef Mehellou PhD Lecturer in Medicinal Chemistry Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University Dr. Mehellou[/caption] Dr. Youcef Mehellou PhD Lecturer in Medicinal Chemistry Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University MedicalResearch.com: What is the background for this study? Response: Over the last decade or two, there has been many reports linking genetic mutations to the pathogenesis of Parkinson’s disease (PD). Among the proteins that have been found to be mutated in PD is a protein called PINK1. Indeed, PINK1 mutations that disturb its function in cells were found to be causal of PD in humans. Subsequent studies showed that PINK1 is a major player in maintaining healthy neurons. This is because it is one of the components involved in controlling the quality of the mitochondria, an organelle within the cell, and it does this by triggering the disposal of unhealthy mitochondria. Overall, studies into PINK1 indicated that the activation of PINK1 as a plausible strategy for maintaining health neurons and hence slowing down the development and progress of Parkinson’s disease.
Author Interviews, Neurological Disorders / 07.12.2017

MedicalResearch.com Interview with: [caption id="attachment_38775" align="alignleft" width="150"]Audrey S. Dickey, Ph.D. Assistant Professor Department of Neurology, DUMC 2900 Durham, NC  27710 Dr. Dickey[/caption] Audrey S. Dickey, Ph.D. Assistant Professor Department of Neurology, DUMC 2900 Durham, NC  27710 MedicalResearch.com: What is the background for this study? What are the main findings? Response: A drug already used to treat certain forms of cancer may also be an effective therapy for Huntington’s disease, according to a new study in the latest issue of Science Translational Medicine. The same study also increases our understanding of how this drug, and other medications like it, may offer hope for other neurodegenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease. Huntington’s disease is a devastating, inevitably fatal disease, with no medications that slow or stop disease progression. In this study, mice with the equivalent of Huntington’s disease became more mobile, recovered from neurodegeneration, and lived longer after being treated with Bexarotene. The same research builds on a 2016 study where Dr. Al La Spada, Dr. Audrey Dickey and colleagues showed that the drug KD3010 is an effective treatment for Huntington’s disease in mice and in human patient neurons made from stem cells.
Author Interviews, Microbiome, Multiple Sclerosis / 23.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38492" align="alignleft" width="170"]Kouichi Ito, PhD Associate Professor Department of Neurology Robert Wood Johnson Medical School Rutgers Dr. Kouichi Ito[/caption] Kouichi Ito, PhD Associate Professor Department of Neurology Robert Wood Johnson Medical School Rutgers MedicalResearch.com: What is the background for this study? What are the main findings? Response: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), and breakdown of immune tolerance to CNS proteins has been suggested to initiate CNS autoimmunity. Although the mechanism underlying the breakdown of immune tolerance to CNS proteins is still unknown, gut microbiota has been suggested to be involved in disease initiation and progression. To investigate the etiology of Multiple Sclerosis, we have created humanized transgenic mice expressing MHC class II and T cell receptor genes isolated from an Multiple Sclerosis patient and showed that gut dysbiosis, alteration in intestinal microbial composition, can induce gut leakiness and subsequently trigger the development of neurological deficits through activation of complement C3 and reduction of CBLB and Foxp3 genes. This study suggests that gut dysbiosis is one of the possible etiological factors for Multiple Sclerosis.
Author Interviews, Cognitive Issues, Dermatology, Infections, Mental Health Research, Neurological Disorders, NIH / 23.11.2017

MedicalResearch.com Interview with: [caption id="attachment_38474" align="alignleft" width="400"]The brain of one patient who died from sporadic Creutzfeldt-Jacob disease (sCJD) appears nearly identical to the brain of a mouse inoculated with infectious prions taken from the skin of patients who died from sCJD. The brain of one patient who died from sporadic Creutzfeldt-Jacob disease (sCJD) appears nearly identical to the brain of a mouse inoculated with infectious prions taken from the skin of patients who died from sCJD.
Case Western Reserve University[/caption]   Byron Caughey, Ph.D. Senior Investigator Chief, TSE/prion Biochemistry Section Laboratory of Persistent Viral Diseases NIH/NIAID Rocky Mountain Laboratories Hamilton, MT      MedicalResearch.com: Would you briefly explain what is meant by Creutzfeldt-Jakob disease? Response: Creutzfeldt-Jakob disease (CJD) is an incurable—and ultimately fatal—transmissible, neurodegenerative disorder in the family of prion diseases. Prion diseases can be found in many mammalian species and are due to the conversion of normally harmless prion protein molecules into abnormally folded, aggregated and self-propagating clusters and filaments in the brain. The accumulation of these clusters has been associated with tissue damage that often leaves dying neurons and microscopic sponge-like holes in the brain. In the sporadic and genetic forms of CJD this pathogenic process appears to arise spontaneously in the patient. However, the transfer of the prion protein aggregates from a Creutzfeldt-Jakob disease patient into another human or experimental animal can initiate the pathogenic process in the recipient. These infectious forms of prion protein are called prions. Human prion diseases include fatal insomnia; kuru; Gerstmann-Straussler-Scheinker syndrome; and variant, familial and sporadic CJD. Sporadic CJD is the most common human prion disease, affecting about one in one million people annually worldwide. Other prion diseases include scrapie in sheep; chronic wasting disease in deer, elk and moose; and bovine spongiform encephalopathy (BSE), or mad cow disease, in cattle.
Author Interviews, Epilepsy, NEJM, Neurological Disorders, Pediatrics, Surgical Research / 25.10.2017

MedicalResearch.com Interview with: Dr. Manjari Tripathi Professor, Epileptology, Neurology Dr. P Sarat Chandra, Chief epilepsy Neurosurgeon AIIMS, New Delhi MedicalResearch.com: What is the background for this study?:
  1. Surgery for drug resistant epilepsy (DRE) is an accepted procedure for children and there have been multiple surgical series and surgical techniques published in literature. However, till date there are no randomized controlled trials (RCT) available to objectively demonstrate the safety and efficacy of surgical therapy in children with DRE. There are till date only 2 randomized trials for adult patients with drug resistant epilepsy (both for mesial temporal sclerosis only, Wiebe S et al, New Eng J Med, 2001 & Engel J et al, JAMA, 2012).
  2. Children constitute a significant proportion of patients undergoing surgical therapy for DRE (close to 50% in tertiary centers). They have unique problems associated due to uncontrolled epilepsy and some of these include epileptic encephalopathy and status epilepticus. In addition, surgery is also associated with problems like hypothermia, issues related to blood loss etc. Thus the senior author (Manjari Tripathi) and her team felt that a RCT would be very important to objectively assess the role of surgery and hence designed this study.
Author Interviews, CDC, JAMA, Neurological Disorders, Zika / 17.10.2017

MedicalResearch.com Interview with: [caption id="attachment_37584" align="alignleft" width="125"]Emilio Dirlikov, PhD Epidemic Intelligence Service Officer CDC  Dr. Dirlikov[/caption] Emilio Dirlikov, PhD Epidemic Intelligence Service Officer CDC  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In December 2015, Puerto Rico Department of Health (PRDH) reported its first confirmed locally acquired case of Zika virus disease. In February 2016, PRDH reported the first person diagnosed with Guillain-Barré syndrome (GBS) who also had evidence of Zika virus infection. At the time, scientific evidence of the potential association between Zika virus infection and GBS was lacking, and rigorous studies were needed. Through a collaboration between PRDH, CDC, and the University of Puerto Rico (UPR), we conducted a case-control study to determine risk factors for GBS during the 2016 Zika virus epidemic. By prospectively enrolling case-patients, we shortened the time to enrollment, increasing the likelihood of detecting Zika virus nucleic acids to confirm Zika virus infection. As a result, we found that an acute Zika virus infection confirmed by laboratory testing is a risk factor for developing Guillain-Barré syndrome. This is the first case-control study to find laboratory evidence showing this given the difficulty of confirming Zika virus infection among people diagnosed with GBS.
Author Interviews, Endocrinology, Epilepsy / 17.10.2017

MedicalResearch.com Interview with: [caption id="attachment_21891" align="alignleft" width="125"]Dr. Samba Reddy, PhD, RPh, FAAPS Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center Bryan, TX Dr. Samba Reddy[/caption] Dr. Samba Reddy, Ph.D., R.Ph., FAAPS, FAAAS, FAES Professor Neuroscience and Experimental Therapeutics College of Medicine Texas A&M University Health Science Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: For the past two decades, D. Samba Reddy, PhD, RPh, professor of neuroscience and experimental therapeutics at the Texas A&M College of Medicine, has been searching for answers to catamenial epilepsy, a subset of chronic epilepsy that causes a dramatic increase in seizures during women’s menstrual periods. Although this condition has been documented for millennia, there is currently no effective treatment for catamenial seizures, leaving many women and their families desperate for answers. In this report, the researchers discovers the neuro-code for treating women with menstrual period-linked epilepsy. A unique platform has been created for clinical trials for catamenial seizures with synthetic neurosteroid agents.
Alzheimer's - Dementia, Author Interviews, Infections, Neurology, Parkinson's / 22.09.2017

MedicalResearch.com Interview with: [caption id="attachment_37066" align="alignleft" width="300"] Under a magnification of 900X, this hematoxylin and eosin-stained (H&E) photomicrograph of a brain tissue specimen revealed a case of neurotoxoplasmosis in a patient who had also been diagnosed with multiple myeloma. Note the Toxoplasma gondii tissue cyst, within which bradyzoites could be seen developing. CDC Image[/caption] Rima McLeod, M.D., F.A.C.P, F.I.D.S.A Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College, Director, Toxoplasmosis Center, Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis, Member Global Health Center, Affiliate CHeSS; Attending Physician, Chicago Medicine, The University of Chicago MedicalResearch.com: What is the background for this study? * One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. * Approximately fifteen million of these have congenital toxoplasmosis. * The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites. * In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process. * Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior. * Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases. * Although neurobehavioral disease is associated with seropositivity, causality is unproven. * Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality. * Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases. * We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design * To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments? * We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions. * To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain. 
Author Interviews, Diabetes, Lancet, Parkinson's / 08.08.2017

MedicalResearch.com Interview with: Dr Dilan Athauda MRCP Sobell Department of Motor Neuroscience and Movement Disorders UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery London MedicalResearch.com: What is the background for this study? Response: Exenatide is a synthetic version of a naturally occurring protein - exendin-4 - that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1).  In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes. Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body.  These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment.  During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival. Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease.  The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections.  However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw. As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial.
Author Interviews, Neurological Disorders, Technology / 29.06.2017

MedicalResearch.com Interview with: [caption id="attachment_35654" align="alignleft" width="200"]Howard Jay Chizeck ScD Professor, Electrical Engineering Adjunct Professor, Bioengineering Co-Director UW Biorobotics Laboratory Graduate Program in Neuroscience UW CoMotion Presidential Innovation Fellow Research Thrust Testbed Co-Leader Prof. Chizeck[/caption] Howard Jay Chizeck ScD Professor, Electrical Engineering Adjunct Professor, Bioengineering Co-Director UW Biorobotics Laboratory Graduate Program in Neuroscience UW CoMotion Presidential Innovation Fellow Research Thrust Testbed Co-Leader MedicalResearch.com: What is the background for this study? What are the main findings? Response: Essential Tremor is treated using Deep Brain Stimulation (DBS) in some patients. Current clinical practice involves Deep Brain Stimulation with an "always on" stimulation. This causes extra battery drain, because stimulation is applied when not needed. Also excessive stimulation is not necessarily a good thing, Our work is aimed at adjusting the stimulation, so that it comes on and turns off only when needed to suppress tremor symptoms.