Author Interviews, Neurological Disorders / 07.12.2016

MedicalResearch.com Interview with: Dr. Paul Davies PhD Tufts University School of Medicine Department of Neuroscience Boston, MA 02111 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Inhibition in the brain regulates neuronal action potential generation, too little inhibition can directly cause conditions such as epileptic seizures, neurodevelopment disorders, and neurodegenerative disorders. The main type of inhibition in the mammalian brain occurs when the neurotransmitter γ-aminobutyric acid (GABA) binds to the GABA type A receptors (GABAARs), a ligand-gated ion channel. Once bound with GABA, the receptor changes shape to open the ion channel allowing negative charged chloride ions to flow through into the cell and inhibiting excitation steaming from positive charged ions flowing through opposing excitatory ion channels. GABAARs mediate both synaptic (phasic) and extrasynaptic (tonic) inhibitory neurotransmission in the CNS and are the sites of action of benzodiazepines, barbiturates, general anesthetics and neuro-active steroids. We have been focused on the extrasynaptic GABAARs that mediate tonic inhibition. In the dentate gyrus of the hippocampus, neocortex, striatum and the thalamus tonic inhibition is largely dependent on GABAARs composed of α4, β2/3, and δ subunits. Neuro-active steroids play a central role in regulating behavior via their ability to allosterically enhance GABAARs, particularly extrasynaptic α4-containing GABAARs. Allosteric enhancement means that neuro-active steroids bind to GABAARs and cause a further change in the structure of the ion channel allowing it to remain open for longer. For the last few decades, allosteric enhancement of GABAARs by neuro-active steroids has been the prevailing explanation for how the steroids increase inhibition in the brain. However, recently we described a new mechanism where the neuro-active steroid, THDOC, increased the association of protein kinase C (PKC) with extrasynaptic α4β3 subunit-containing GABAARs. The increase in PKC-mediated phosphorylation of α4 and β3 subunits leads to an increase in membrane insertion from intracellular stores, an increase in GABAAR stability in the membrane, and a prolonged increase of tonic inhibition, even after when the neuro-active steroids have been removed. For this present study we asked whether other neuro-active steroids demonstrated the same metabotropic activity. We tested another endogenous neuro-active steroid, allopregnanolone (ALLO), and the synthetic neuro-active steroid, ganaxolone. In collaboration with SAGE Therapeutics, we also tested another synthetic neuro-active steroid, SGE-516. We found that all the neuro-active steroids tested were able to allosterically potentiate both synaptic and, to a lesser degree, extrasynaptic GABAARs. Short 15-minute exposures to neuro-active steroids resulted in significantly increase in phosphorylation of β3 subunits, and long lasting enhancement of tonic current. These increases were metabotropic in nature, being dependent upon PKC mediated phosphorylation. Following this short 15-minute exposure we saw a change in synaptic currents only with SGE-516 suggesting a selectivity of this metabotropic pathway to extrasynaptic GABAARs. Although ganaxolone was an effective allosteric modulator, it did not produce a metabotropic enhancement of tonic current suggesting that not all neuroactive steroids work through this pathway. (more…)
Author Interviews, Brigham & Women's - Harvard, ENT, Neurological Disorders / 30.11.2016

MedicalResearch.com Interview with: Daniel M. Merfeld, Ph.D. Professor of Otolaryngology Harvard Medical School Massachusetts Eye and Ear Director, Jenks Vestibular Physiology Laboratory Senior Scientist MedicalResearch.com: What is the background for this study? Response: Nearly half of the population will see a clinician at some point in their lives with symptoms related to the vestibular system (e.g., dizziness, vertigo, imbalance and blurred vision). The vestibular system, made up of tiny fluid-filled membranes in the inner ear, is responsible for receiving information about motion, balance and spatial orientation. With the goal of determining whether age affected the function of the vestibular system, our research team administered balance and motion tests to 105 healthy people ranging from 18 to 80 years old and measured their vestibular thresholds (“threshold” refers to the smallest possible motion administered that the subject is able to perceive correctly). (more…)
Author Interviews, JAMA, Neurological Disorders, Radiology, UCLA / 28.11.2016

MedicalResearch.com Interview with: Joseph O’Neill, PhD Division of Child and Adolescent Psychiatry University of California–Los Angeles Semel Institute for Neuroscience Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: Stuttering seriously diminishes quality of life. While many children who stutter eventually grow out of it, stuttering does persist into adulthood in many others, despite treatment. Like earlier investigators, we are using neuroimaging to explore possible brain bases of stuttering, aiming, eventually, to improve prognosis. What's novel is that our study deploy neuroimaging modalities-- arterial spin labelling and, in this paper, magnetic resonance spectroscopy (MRS)-- not previously employed in stuttering. MRS offers prospects of detecting possible neurochemical disturbances in stuttering. The MRS results showed differences in neurometabolite-- brain chemicals-- levels between people who stutter (adults and children) and those who don't in many brain regions where other neuroimaging has also observed effects of stuttering. In particular, MRS effects were apparent in brain circuits where our recent fMRI work detected signs of stuttering, circuits subserving self-regulation of speech production, attention and emotion. This reinforces the idea that stuttering has to do with how the brain manages its own activity along multiple dimensions: motivation, allocation of resources, and behavioral output. (more…)
Author Interviews, Neurological Disorders, Ophthalmology, Pediatrics / 23.11.2016

MedicalResearch.com Interview with: Marius George Linguraru, DPhil, MA, MB Principal Investigator Associate Professor of Pediatrics and Radiology George Washington University School of Medicine and Health Sciences Children’s National Health System Washington, DC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome affecting the central nervous with an incidence of one in 3,000 births. Nearly one in five children with NF1 develops an optic pathway glioma (OPG), a low-grade tumor of the anterior visual pathway (i.e., optic nerves, chiasm and tracts). These tumors are not amenable to surgical resection and can cause permanent vision loss ranging from a mild decline in visual acuity to complete blindness. Only half of children with NF1-OPGs will experience vision loss, typically between 1 to 6 years of age. The other half will never lose vision or require treatment. All previous studies have consistently demonstrated that the change in NF1-OPG size is not related to the clinical outcome. For example, the optic pathway glioma size may be stable or even decrease, yet the vision will decline. Alternatively, the OPG size may increase, yet the clinical outcome remains stable or even improves. As no imaging or clinical features can identify which children with NF1-OPGs will ultimately lose vision, clinicians struggle to follow these children and decide when to intervene. We used quantitative imaging technology to accurately assess in magnetic resonance imaging (MRI) the total volume of OPGs in NF1. We also determined the retinal nerve fiber layer thickness in these children, a measure of axonal degeneration and an established biomarker of visual impairment. The results were outstanding, as we showed for the first time that the volume of an optic pathway glioma is indeed correlated with the likelihood of vision loss in children with Neurofibromatosis type 1. (more…)
ADHD, Author Interviews, JAMA, Neurological Disorders, NIH / 22.11.2016

MedicalResearch.com Interview with: Gustavo Sudre, PhD Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch National Human Genome Research Institute Bethesda, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Response: ADHD is the most common childhood neuropsychiatric disorder, affecting 7-9% of school age children. It is highly heritable (h2=0.7), but few risk genes have been identified. In this study, we aimed to provide quantitative brain-based phenotypes to accelerate gene discovery and understanding. ADHD is increasingly viewed as resulting from anomalies of the brain’s connectome. The connectome is comprised of the structural connectome (white matter tracts joining different brain regions) and the functional connectome (networks of synchronized functional activity supporting cognition). Here, we identified features of the connectome that are both heritable and associated with ADHD symptoms. (more…)
Author Interviews, Immunotherapy, Multiple Sclerosis / 22.11.2016

MedicalResearch.com Interview with Ralph Kern, M.D. Senior vice president, Worldwide Medical Biogen MedicalResearch.com: What is the background for this study? Response: Previously reported clinical trials of daclizumab demonstrated significant efficacy across clinical and MRI measures, compared to placebo and interferon beta-1a 30 mcg intramuscular (IM) injection, and established the therapy’s safety profile for up to two to three years. These trials were the basis for approval by health authorities in the United States, European Union and Australia. Daclizumab is a once-monthly, self-administered, subcutaneous therapy for relapsing forms of MS (RMS). At ECTRIMS we presented the first interim results from EXTEND, a long-term extension study. EXTEND is an ongoing multicenter, open-label study to evaluate the safety and efficacy of daclizumab treatment in more than 1,500 patients with RMS. This interim ECTRIMS analysis includes up to five years of data from patients who were previously enrolled in DECIDE. DECIDE was a Phase 3 study evaluating the effects of daclizumab relative to interferon beta-1a IM. In the new analysis, patients who were treated with interferon beta-1a IM for two to three years in DECIDE switched to daclizumab when they enrolled in EXTEND, and were compared to daclizumab patients treated continuously in both DECIDE and EXTEND. (more…)
Author Interviews, JAMA, Neurological Disorders, Parkinson's / 21.11.2016

MedicalResearch.com Interview with: Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with SPG 11 mutations can present with motor symptoms characterized by juvenile onset dystonia, Parkinsonism and lower extremity spasticity. Parkinsonism appears to be responsive to levodopa therapy early in the disease but treatment is complicated by the occurrence of motor fluctuations resembling parkinson disease. Patients have short duration of medication effects, unpredictable response to medications along with generalized, excessive involuntary movements known as dyskinesias. Deep Brain stimulation is a well-established treatment for movement disorders but it has never been used in this disease. We first report the clinical outcome obtained with globus pallidus internal deep brain stimulation in a patient with parkinsonism, dystonia, dyskinesias related to SPG 11. Additionally, we report for the first time the basal ganglia changes observed in the disease using intraoperative neuronal recordings. Patient had a sustained and remarkable response to stimulation over the next two years without side effects. Neurophysiologic changes revealed a unique pattern of neuronal firing despite of the resemblance to advance Parkinsons disease. (more…)
ALS, Author Interviews, NEJM, Technology / 19.11.2016

MedicalResearch.com Interview with: Mariska Van Steensel PhD Nick F. Ramsey, Ph.D. Department of Neurology and Neurosurgery Brain Center Rudolf Magnus University Medical Center Utrecht Utrecht, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who are severely paralyzed due to for example ALS or brain stem stroke are often unable to speak (also called ‘ Locked-in State'), and therefore need assistive devices, such as an eye tracker, for their communication. When these devices fail (e.g. due to environmental lighting or eye movement problems), people may indicate yes or no with eye blinks in response to closed questions. This leaves patients in a highly dependent position, since questions asked may or may not represent their actual wish or comment. In the current study, we used a technology called brain-computer interfacing (BCI), to allow a patient with late-stage amyotrophic lateral sclerosis (ALS) to control a communication device using her brain signals. The patient was implanted with subdural electrodes that covered the brain area that is normally responsible for hand movement. The electrodes were connected with wires, subcutaneously, to an amplifier/transmitter device that was placed subcutaneously under the clavicle. The patient was able to generate a signal equivalent to a mouse-click with this brain-computer interface by attempting to move her hand, and used it to make selections of letters or words on her communication device, with high accuracy and a speed of 2 letters per minute. She used the brain-computer interface system to communicate whenever she was outside, as her eye-tracker device does not function well in that situation. (more…)
Author Interviews, Brigham & Women's - Harvard, Neurological Disorders / 17.11.2016

MedicalResearch.com Interview with: Michael D. Fox, MD, PhD Assistant Professor in Neurology Berenson-Allen Center for Noninvasive Brain Stimulation Division of Cognitive Neurology, Department of Neurology Beth Israel Deaconess Medical Center Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Consciousness is thought to be composed of arousal plus awareness, but no one knows where these processes live in the human brain. We took a unique approach to this question by studying human brain lesions that disrupt consciousness and cause coma. We found one small spot in the brainstem that was specific for coma (i.e. lesions that hit this spot caused coma while lesions that didn’t hit the spot did not cause coma). In other words, there was one spot in the human brainstem that, when lesioned, disrupted arousal and caused coma We then looked at the connectivity of that brainstem spot, and found that it was connected to two cortical regions previously implicated in awareness. These cortical regions also contained a unique type of brain cell thought only to be present in higher order mammals that are self-aware. To confirm our findings, we looked at the integrity of our network in patients with disorders of consciousness (e.g. persistent vegetative state) and found selective disruption of this network. (more…)
Author Interviews, Hepatitis - Liver Disease, JAMA, Neurological Disorders / 08.11.2016

MedicalResearch.com Interview with: Philip Van Damme, MD, PhD Department of Neurology and Department of Neurosciences, Experimental Neurology KU Leuven University of Leuven VIB, Vesalius Research Center, Leuven, Belgium Philip Van Damme, MD, PhD Department of Neurology and Department of Neurosciences, Experimental Neurology KU Leuven University of Leuven VIB, Vesalius Research Center, Leuven, Belgium MedicalResearch.com: What is the background for this study? Response: The hepatitis E virus (HEV) has been discovered more that 60 years ago. Its clinical manifestations are usually self-limiting and mild. More recently, several immune-mediated neurological complications of this virus have been described, such as the Guillain-Barre syndrome (GBS) and neuralgic amyotrophy. In this study, we investigated the frequency of a preceding HEV infection in patients presenting with a GBS syndrome or one of its less common disease variants. At the same time, we tested for other known pathogens known to be associated with GBS. (more…)
Author Interviews, Neurological Disorders / 04.11.2016

MedicalResearch.com Interview with: Nir Lahav Physics Department Bar-Ilan University in Israel MedicalResearch.com: What is the background for this study? Response: Our brain is a very complex network, with approximately 100 billion neurons and 100 trillion synapses between the neurons. The question is how can we cope with this enormous complexity? Ultimately, scientists seek to understand how a global phenomenon such as consciousness can emerge from our neuronal network. We used network theory in order to cope with this complexity and to determine how the structure of the human cortical network can support complex data integration and conscious activity. Previous studies have shown that the human cortex is a network with small world properties, which means that it has many local structures and some shortcuts from global structures which connect faraway areas (similar to the difference between local buses and cross-country trains). The cortex also has many hubs, which are nodes that have a high number of links (like central stations), that are also strongly interconnected between themselves, making it easy to travel between the brain's information highways.But in order to examine how the structure of the network can support global emerging phenomena, like consciousness, we need to look not only in the different nodes. We need to check global areas with lots of nodes. That's why we applied a network analysis called k-shell decomposition. This analysis takes into account the connectivity profile of each node making it easy to uncover different neighborhoods of connections in the cortical network, we called shells. The most connected neighborhood in the network is termed the network's nucleus. until today scientists were only interested in the network's nucleus, but we found that these different shells can hold important information about how the brain integrates information from the local levels of each node to the entire global network. For the first time we can build a comprehensive topological model of our cortex. (more…)
ALS, Antioxidants, Author Interviews, Columbia, Inflammation, JAMA, Nutrition / 26.10.2016

MedicalResearch.com Interview with: Dr. Jeri Nieves PhD Director of bone density testing New York's Helen Hayes Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Amyotrophic lateral sclerosis (ALS) is a devastating severe neurodegenerative disorder that causes progressive muscle atrophy, paralyses, and eventual respiratory failure. Our objective was to evaluate the associations between nutrition and severity of ALS around the time of diagnosis. This was a cross-sectional analysis of data from a multicenter cohort of 302 patients with ALS. We assessed nutrient intake using a modified Block Food Frequency Questionnaire. The outcomes were respiratory function (measured using percentage forced vital capacity; FVC%) and functional performance measured by ALS Functional Rating Scale–Revised (ALSFRS-R), both considered important indicators of the severity of ALS. Results of the regression analysis were that higher intakes of antioxidants and carotenes from vegetable intake were associated with higher ALSFRS-R scores or better %FVC. We used a novel analysis to evaluate the diet as a whole and found that higher intakes of antioxidants, fiber from grains, vegetables, fruit, eggs, fish, and poultry were all associated with higher function in patients with ALS. However, milk and lunch meats were associated with lower measures of function. These consistent results from two different statistical analyses indicate that diet may help minimize the severity of ALS. Perhaps these findings point to the role of oxidative stress in ALS severity. In summary, increased consumption of antioxidant nutrients, foods high in carotenoids and fiber, vegetables and fruits, poultry and fish are associated with better function around the time of ALS diagnosis. (more…)
Author Interviews, Neurological Disorders, Pulmonary Disease / 24.10.2016

MedicalResearch.com Interview with: Paolo Prandoni, M.D., Ph.D. and Department of Cardiovascular Sciences Vascular Medicine Unit University of Padua, Padua Sofia Barbar, M.D Department of Internal and Emergency Medicine Civic Hospital of Camposampiero Camposampiero MedicalResearch.com: WhaWhat are the main findings? Response: Syncope is defined as a sudden loss of consciousness due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. According to the most recent guidelines, syncope can be classified as neurally-mediated, due to orthostatic hypotension and cardiovascular. Syncope is frequent in general population and represents up to 2% of all attendances in Emergency Department in Europe. The initial approach is unable to identify a plausible cause for syncope in 25-30% of cases and approximately 40% of syncope referred to an Emergency Department is then admitted to the hospital. Pulmonary embolism (PE) is an obstruction in the pulmonary arteries interfering with both blood circulation and gas exchange and therefore representing a potentially life-threatening event. Clinical features of PE are extremely variable. Available guidelines on syncope management consider PE as an infrequent cardiovascular cause of syncope. However, the true prevalence of pulmonary embolism in syncope-patients it is actually unknown. Moreover a workup for PE diagnosis in these patients is not suggested in the current guidelines. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Neurological Disorders / 20.10.2016

MedicalResearch.com Interview with: Dr David Lynch MB, MRCPI Leonard Wolfson Clinical Fellow UCL Institute of Neurology Queen Square, London MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2011 it was discovered that mutations in a gene called CSF1R cause a rare syndrome of early onset dementia often accompanied by movement disorders, spasticity and seizures, which is named adult onset leukoencephalopathy with axonal spheroids (ALSP). The hallmarks of ALSP are a characteristic appearance on MRI imaging and findings in brain pathological specimens - axonal swellings or 'spheroids'. We manage a multidisciplinary group with expertise in leukoencephalopathies and have previously identified patients with mutations in CSF1R. However, we also found patients with a syndrome typical of ALSP who did not carry mutations in CSF1R. In this study, we showed that some of these patients carry recessive mutations in a different gene, AARS2. This included a patient with characteristic axonal spheroids in brain tissue and typical ALSP clinical and imaging features. (more…)
Author Interviews, Parkinson's, Pharmacology / 28.09.2016

MedicalResearch.com Interview with: Rosa & Co. LLC,Dr. Christina Friedrich Chief Engineer, PhysioPD Rosa & Co. LLC MedicalResearch.com: What is the background for this study? Response: Elan was developing compounds for the treatment of Parkinson’s Disease. The compounds were designed to modify negative effects of alpha-synuclein on neurotransmitter vesicle trafficking, but these effects are poorly understood. Elan and Rosa collaborated in the development of a Synuclein PhysioMap®, a graphical model architecture to support hypothesis generation and testing. The objectives of the project were to provide insight into alpha-synuclein function in vesicle trafficking, memorialize and communicate the current state of knowledge within Elan, and to recommend experiments to test hypotheses, resolve uncertainties and identify and prioritize potential targets. (more…)
Author Interviews, Multiple Sclerosis, Pharmacology / 27.09.2016

MedicalResearch.com Interview with: Marcia Kayath, MD Vice President and Head US Clinical Development and Medical Affairs US General Medicines Novartis Pharmaceuticals Corporation MedicalResearch.com: What is the background for this study? What are the main findings? Response: Injectable disease-modifying therapies (DMTs) are typically used first-line in patients with multiple sclerosis (MS), but discontinuation of injectable DMTs is common, especially within the first 12 months of treatment1,2. PREFERMS is the largest, prospective, randomized, active-controlled, open-label study to evaluate patient retention in patients with relapsing-remitting multiple sclerosis (RRMS). In the 12-month, Phase IV study, a total of 875 patients were randomized (1:1) to Gilenya® (fingolimod) 0.5 mg or to a pre-selected injectable DMT (IFNβ-1a, IFNβ-1b or glatiramer acetate), and followed up quarterly for 12 months3. After a minimum of 3 months of treatment, a single on-study treatment switch was allowed, however, switches due to efficacy or safety were allowed (based on patient-doctor consultation) at any month following randomization3. The primary endpoint was to compare the patient retention on randomized treatment over 12 months3. This study was powered for the primary endpoint (retention rate)3. The study was not powered to detect the treatment difference in the secondary efficacy endpoints or treatment effects related to switching study medication3. (more…)
Author Interviews, Biomarkers, JAMA, NIH, Parkinson's / 26.09.2016

MedicalResearch.com Interview with: Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland MedicalResearch.com: What is the background for this study? Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls. (more…)
Author Interviews, Epilepsy, JAMA, Mayo Clinic, Neurological Disorders / 23.09.2016

MedicalResearch.com Interview with: Brian Nils Lundstrom, MD, PhD Department of Neurology Mayo Clinic Rochester, Minnesota MedicalResearch.com: What is the background for this study? What are the main findings? Response: About as many people have drug-resistant focal epilepsy as have multiple sclerosis, and treatment options are limited. This study describes an alternative treatment option that has proven very helpful for the majority of participants. Electrical stimulation is delivered continuously via implanted electrodes to the region of brain where seizures start. The electrical stimulation decreases the seizure-related discharges from the brain, and for about 40% of patients their disabling seizures were completely stopped. (more…)
Author Interviews, Neurological Disorders / 31.08.2016

MedicalResearch.com Interview with: Sanne Kikkert, DPhil student FMRIB Centre, University of Oxford Oxford, United Kingdom MedicalResearch.com: What is the background for this study? Response: One of the most mysterious questions about the brain’s ability to adaptively change to new circumstances is: what happens to the brain once a key input is lost (e.g. through amputation)? It has been thought that the hand representation in the brain, located in the primary somatosensory cortex, is maintained by regular sensory input from the hand. Indeed, textbooks teach that any sensory representation in the brain will be ‘overwritten’ if its primary input stops. Following this explanation, people who have undergone hand amputation would show extremely low or no activity related to its original focus in the brain area of the missing hand. However, we know that amputees often experience phantom sensations from their missing hand, such that when asked to move a phantom finger they can ‘feel’ that movement. We previously showed that we can trace some activity in the missing hand brain area when amputees move their phantom hand. In this study, we were interested in finding how the representation of a missing hand is stored in the brain. (more…)
Author Interviews, Genetic Research, Neurological Disorders / 26.08.2016

MedicalResearch.com Interview with: Lee Henderson, Ph.D. CEO Vybion, Inc. Ithaca, NY 14852Lee Henderson, Ph.D. CEO, Vybion, Inc. Ithaca, NY 14852 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease characterized by loss of both cognitive and motor function as a result of neuron loss primarily within the brain striatum. HD is directly caused by the expansion of CAG repeats in the huntingtin gene resulting in an expanded glutamine region (polyQ) near the N-terminus of the protein. Age of disease onset and the rate of progression is directly correlated to the size of the expansion with pathology observable at 35-70 repeats in adults and greater in juvenile onset. During normal turnover and degradation of the huntingtin protein, the N-terminal polyQ-containing fragments drive pathology and aggregate formation in cells. The direct link to progression has been described by several laboratories using cell-based and animal model studies and confirmed in humans as the binding of these N-terminal fragments to DNA and transcription factors that result in widespread gene dysregulation in neurons. (more…)
Author Interviews, NEJM, Neurological Disorders, Surgical Research / 12.08.2016

MedicalResearch.com Interview with: Gil I. Wolfe, MD, FAAN Irvin and Rosemary Smith Professor and Chair Dept. of Neurology/Jacobs Neurological Institute Univ. at Buffalo Jacobs School of Medicine and Biomedical Sciences/SUNY Buffalo General Medical Center Buffalo, NY 14203-1126 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thymectomy has been used in myasthenia gravis (MG), in particular those patients who do not have a tumor of the thymus gland, known as a thymoma, for over 75 years without randomized data to support its use. A practice parameter in 2000 on behalf of the American Academy of Neurology stated that the benefits of thymectomy in this population of non-thymomatou smyasthenia gravis patients remained uncertain, classified thymectomy as a treatment option in this group, and called for rigorous, randomized studies. What we found is that compared to an identical prednisone protocol alone, that extended transsternal thymectomy confers significant benefits to non-thymomatous MG patients over a period of three years after the procedure. The benefits include better disease status, reduced prednisone requirements, fewer hospitalizations to manage  myasthenia gravis worsenings, and a lower symptom profile related to side effects from medications used to control the disease state. (more…)
Aging, Author Interviews, Neurological Disorders, Weight Research / 06.08.2016

MedicalResearch.com Interview with: Dr. Lisa Ronan, PhD Department of Psychiatry University of Cambridge Neuroscience MedicalResearch.com: What is the background for this study? What are the main findings? Response: A growing body of literature relates common markers of aging to those observed in obesity and supports the hypothesis that obesity may accelerate or advance the onset of brain aging. To investigate this relationship at a population level we analysed the white matter volume of the brain in 473 adult subjects ages 20 - 87 years and contrasted these volumes between subjects who were lean (BMI between 18.5 - 25) and those who were overweight / obese (BMI > 25). Our results suggest that the latter group had significantly smaller white matter volumes when compared to their lean age-matched counterparts. We found that this difference in volume equated to a brain-age increase of 10 years in the overweight / obese group. We found no evidence that obesity impacted on cognitive ability. (more…)
Alzheimer's - Dementia, Author Interviews, Neurological Disorders / 05.08.2016

MedicalResearch.com Interview with: Auriel Willette, PhD Assistant Professor Departments of Food Science and Human Nutrition, and Psychology Iowa State University MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Alzheimer's disease (AD) field continues to look for biological markers that can detect onset and progression of the disease, mainly memory decline and atrophy of medial temporal lobe where conscious memories are formed. The immune system has long been known to affect the onset and progression of Alzheimer's disease (AD), usually through a process called inflammation in the brain that causes damage to brain cells called neurons. We wished to examine all available immune system data in a large, well-established cohort across the AD spectrum and discover which immune markers best explained memory decline and medial temporal atrophy over 2 years. In essence, among dozens of candidate immune markers, we consistently found two to be most relevant: neuronal pentraxin 2 (NPTX2) and chitinase-3-like-protein-1 (C3LP1). NPTX2 is important for facilitating communication between neurons, whereas C3LP1 is related to activation of a part of the immune system that causes inflammation in the brain. To our surprise, higher NPTX2 levels at baseline were potently related to less memory loss and less medial temporal atrophy over 2 years. C3LP1, by contrast, was a relatively poor predictor. NPTX2 also better predicted levels of amyloid and tau in the brain, which are generally thought to help cause AD. Finally, we found that more years of education led to higher NPTX2 levels, suggesting that more formal learning leads to more stable, stronger connections between neurons that give rise to memory. (more…)
Author Interviews, Neurological Disorders, PLoS / 21.07.2016

MedicalResearch.com Interview with: Zoltan Toroczkai, PhD, Professor of Physics Concurrent Professor of Computer Science and Engineering Physics Department University of Notre Dame, Notre Dame, IN, 46556 MedicalResearch.com: What is the background for this study? Response: The mammalian brain is arguably the most complex information processing network and with billions of neurons and trillions of connections it presents formidable challenges to deciphering its fundamental mechanisms for information processing. In the brain, information is encoded into the spatio-temporal firing patterns of groups of neurons (population coding), making the connectivity structure of the network crucial for brain function. Damages to this network have been associated with diseases such as Alzheimer’s, autism and schizophrenia, and thus understanding the cortical network would also help better understand certain diseases of the brain. An experimentally and computationally more feasible approach is to study the anatomical (physical connectivity) network between the functional areas of the cortex, a mosaic of brain patches, each associated with a specific function (e.g., visual, auditory, somatosensory). Based on phylogenic considerations one expects the existence of common fundamental network architectural (and implicitly, processing) principles to be present in all mammalian brains. However, the mammalian brain spans over five orders of variation in size and thus it is not clear at all what are this common architectural features and how would we find them. The challenge here is to compare networks of the same nature (information processing type) but of different orders, with different nodal identities, and of very different spatial embedding (geometrical size) properties. (more…)
Author Interviews, Education, Memory, Neurological Disorders / 15.07.2016

MedicalResearch.com Interview with: Kalipada Pahan, Ph.D Floyd A. Davis, M.D., Endowed Chair of Neurology Professor, Departments of Neurological Sciences, Biochemistry and Pharmacology Rush University Medical Center VA Scientist, Jesse Brown VA Medical Center Chicago, IL 60612 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Individual difference in learning and educational performance is a global issue. In many cases between two students of the same background studying in the same class, one turns out to be a poor learner and does worse than the other academically. Little is known on what changes occur in the brain of poor learners and how to improve performance in poor learners. Here, we have demonstrated that cinnamon, a common food spice and flavoring material, converts poor learning mice to good learners. Results of the study were recently published in the Journal of Neuroimmune Pharmacology. (more…)
Author Interviews, Brigham & Women's - Harvard, Neurological Disorders / 15.07.2016

MedicalResearch.com Interview with: Aleksey G. Kazantsev, PhD Associate Professor in Neurology, Harvard Medical School Drug Discovery Laboratory MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is no cure (disease modify therapy) for any neurodegenerative disorders (ND), most common Alzheimer’s and Parkinson’s or orphan like Huntington’s diseases. Numerous studies show that the pathologies of neurodegenerative diseases at molecular levels are similar but highly complex. No single neurodegenerative mechanism has emerged as predominant, slowing a development of efficient therapy. While gene and cell-based therapeutic approaches are still evolving, we relay on discovery of small molecule drugs as essentially the only strategy with approved track record in human subjects. However, so far a traditional approach of targeting single cellular pathway was unsuccessful for CNS drug development. The current study demonstrated a novel approach of using small molecule with multiple putative neuroprotective activities, which is essentially a combinatorial approach to use compound distinct activities to ameliorate/bock/prevent not one, but a few neurodegenerative pathways. (more…)
Alzheimer's - Dementia, Author Interviews, Chemotherapy, Parkinson's / 13.07.2016

MedicalResearch.com Interview with: Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC. MedicalResearch.com: What is the background for this study? What are the main findings? Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated. Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer's Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau). (more…)
Addiction, Alcohol, Author Interviews, Neurological Disorders / 11.07.2016

MedicalResearch.com Interview with:, Jun Wang, M.D., Ph.D. Assistant Professor Department of Neuroscience and Experimental Therapeutics Interdisciplinary Program in Neuroscience (TAMU/TAMHSC) TAMHSC COLLEGE OF MEDICINE Bryan, TX 77807 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Alcohol use disorder is a big problem for our society and only a limited number of medicine is available. We hope to find more treatment in animal models of alcoholism. A group of neurons containing dopamine D2 receptors in the brain prevent us from drinking alcohol heavily. (more…)
Alzheimer's - Dementia, Author Interviews, Brain Injury, JAMA, Parkinson's / 11.07.2016

MedicalResearch.com Interview with: Paul K. Crane, MD MPH Professor Department of Medicine Adjunct Professor Department of Health Services University of Washington MedicalResearch.com: What is the background for this study? Response: The background is that the most common experience of head injury with loss of consciousness is an apparent recovery. Sometimes this is very fast, sometimes it takes somewhat longer, but typically people return to their prior baseline. Nevertheless there is concern that the head injury may have set in motion processes that would lead to late life neurodegenerative conditions. This is bad enough for someone to deal with but it's made even worse if the head injury isn't even the victim's fault. Previous research has focused especially on Alzheimer's disease. A more limited research has focused on Parkinson's disease. We used data from three prospective cohort studies that included more than 7,000 people to study the relationship between head injury with loss of consciousness and subsequent risk of Alzheimer's and Parkinson's disease. We collected head injury exposure data at study enrollment, at a time when we administered cognitive tests and knew they did not have dementia, so our exposure data are not biased. Each of these studies also performed brain autopsies on people who died, and we evaluated data from more than 1500 autopsies. (more…)
Author Interviews, JAMA, MRI, Parkinson's / 06.07.2016

MedicalResearch.com Interview with: Blayne Welk, MD, MSc,FRCSC Assistant Professor of Surgery Western University London, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior research has demonstrated that gadolinium, which may be used during MRI scans to help visualise the body organs, can be deposited in the body, and remain there for years. The US FDA released a notice last year stating that further research was needed to evaluate the clinical implications of these brain deposits. One of the areas that gadolinium is deposited is the brain, specifically in two regions which control voluntary movement (the globus pallidus and dentate nucleus). Damage to these areas could cause symptoms of Parkinsonism. We used administrative data from Ontario, Canada to evaluate whether people who underwent MRI scans with gadolinium had a higher risk of developing Parkinsonism in the future. In this study, we did not demonstrate an increased risk of Parkinsonism in patients exposed to gadolinium. (more…)