Errors in Dementia Drugs Surprising Common in Parkinson’s Disease

MedicalResearch.com Interview with:

Allison W. Willis, MD, MS Assistant Professor of Neurology Assistant Professor of Biostatistics and Epidemiology Senior Fellow, Leonard Davis Institute Senior Scholar, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania School of Medicine

Dr. Willis

Allison W. Willis, MD, MS
Assistant Professor of Neurology
Assistant Professor of Biostatistics and Epidemiology
Senior Fellow, Leonard Davis Institute
Senior Scholar, Center for Clinical Epidemiology and Biostatistics
University of Pennsylvania School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study was motivated by my own experiences as a neurologist-neuroscientist.

I care for Parkinson disease patients, and over the year, have had numerous instances in which a person was taking a medication that could interact with their Parkinson disease medications, or could worsen their PD symptoms.
Continue reading

Retrotope Expands Compassionate Use Access to RT001 for Amyotrophic Lateral Sclerosis

MedicalResearch.com Interview with:
RetrotopeRobert J Molinari, Ph.D.

President and CEO
Retrotope, Inc.

 

MedicalResearch.com: What is the background for this study?
How does RT001 differ from other treatments for neurodegenerative diseases? 

Response: Lipid peroxidation in critical cell and mitochondrial membranes represents a common pathway of cell death in many neurodegenerative diseases, regardless of the initiating trigger of original damage, e.g. aberrant gene expression, misfolded proteins such as tau and amyloid, environmental insults, etc. This hypothesis was supported by work showing that stabilizing lipids (using virtually indistinguishable isotopic variants of the original dietary molecules) was able to mitigate disease-related cell dysfunction, and reverse disease in a variety of animal models, and more recently, in human patients enrolled in clinical trials.

It has been known for decades that lipid peroxidation detritus of oxidized membrane fats are present in most all diseases of degeneration and aging, including Alzheimer’s disease, Parkinson’s disease, atherosclerosis, ALS, Huntington’s, and fatal inborn genetic errors resulting in neurodegenerative diseases (among others). The hypothesis that controlling such oxidation could provide therapeutic benefit was abandoned when numerous formal trials of classical antioxidants, e.g. Co-enzyme Q, Vitamin E, and others failed to provide meaningful benefit. We believed that the antioxidant mechanism used to attempt control of the membrane oxidation was flawed, but that the target itself was correct. Indeed, by using a new class of oral drugs that are lipids fortified against damage at the key susceptible bonds, we observed reduction in lipid peroxidation damage that halted, and even reversed neurodegenerative disease progression. Dosed in amounts and forms similar to omega 3 and 6 supplements, these drugs exhibited profound disease modification across a broad range of diseases in animal models, placebo controlled- and open label- human trials. Continue reading

Physical Activity Could Reduce Risk of Parkinson disease, esp. in Men

MedicalResearch.com Interview with:
Fudi Wang, M.D., Ph.D. Qiushi Chair Professor Nutrition Discovery Innovation Center School of Public Health/School of Medicine Zhejiang University Hangzhou 310058, ChinaFudi Wang, M.D., Ph.D.
Qiushi Chair Professor
Nutrition Discovery Innovation Center
School of Public Health/School of Medicine
Zhejiang University
Hangzhou  China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Parkinson disease (PD) is the second most common neurodegenerative disease affecting approximately 10 million people around the world. To date, the cause of PD remains poorly understood. It is reported that 90% PD cases have no identifiable genetic cause. What’s worse, few therapeutic advances for the treatment of PD have been made in the past decades. Nevertheless, growing prospective longitudinal studies shed lights on the potential beneficial effect of lifestyle factors on reducing the risk of developing Parkinson disease. In this study, we performed a a dose-response meta-analysis of more than half a million participants.

We found that physical activity, particularly moderate to vigorous physical activity, could significantly reduce PD risk.

Continue reading

Ibudilast Slowed Brain Atrophy Progressive Multiple Sclerosis in Phase 2 Study

MedicalResearch.com Interview with:

Robert J. Fox, MD, FAAN Principal Investigator | SPRINT-MS Trial Mellen Center for MS  |  Cleveland Clinic Cleveland, OH 44195  

Dr. Fox

Robert J. Fox, MD, FAAN
Principal Investigator | SPRINT-MS Trial
Mellen Center for MS  |  Cleveland Clinic
Cleveland, OH 44195 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The current treatment options for progressive multiple sclerosis are very limited. The SPRINT-MS trial sought to obtain proof-of-concept evidence that ibudilast has beneficial activity in progressive multiple sclerosis. In a placebo-controlled, 96-week trial of 255 people living with progressive MS, treatment with ibudilast slowed the progression of brain atrophy (brain shrinkage) by 48% compared to placebo. Side-effects of ibudilast included gastrointestinal symptoms, headache, and depression. 

Continue reading

Maybe Spinal Repair Cells Can Be Turned On and Off

MedicalResearch.com Interview with:

Pier Lorenzo Puri, M.D PhD Professor in the Development, Aging and Regeneration Program Sanford Burnham Prebys Medical Discovery Institute 

Dr. Puri

Pier Lorenzo Puri, M.D PhD
Professor in the Development, Aging and Regeneration Program
Sanford Burnham Prebys Medical Discovery Institute 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: My lab has been studying special repair cells called fibro-adipogenic progenitors (FAPs) and how these cells change in models of motor neuron diseases. These cells usually repair muscles after acute injury. But we are finding the FAPs change dramatically in disease settings.

In this study we looked at these cells in models of spinal cord injury, ALS and spinal muscular atrophy, including muscle tissue from ALS patients. We found that FAPs change radically in several ways.

Most importantly, the cells used a different signaling pathway, IL-6-STAT3, and when we blocked this signaling muscle atrophy and fibrosis halted. While further studies in humans are needed, this is a promising finding as FDA-approved medicines that block IL-6 and STAT3 are available.  Continue reading

Multimodal Imaging Can Personalize and Predict Therapeutic Needs

MedicalResearch.com Interview with:

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

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.   Continue reading

Trial of Antibody Immunotherapy in Parkinson’s Disease

MedicalResearch.com Interview with:

Joseph Jankovic, MD Professor of Neurology  Distinguished Chair in Movement Disorders  Director, Parkinson’s Disease Center  and Movement Disorders Clinic  Department of Neurology                                    Baylor College of Medicine  Baylor St. Luke’s Medical Center at the McNair Campus Houston, TX 77030-4202

Dr. Jankovic

Joseph Jankovic, MD
Professor of Neurology
Distinguished Chair in Movement Disorders
Director, Parkinson’s Disease Center
and Movement Disorders Clinic
Department of Neurology
Baylor College of Medicine
Baylor St. Luke’s Medical Center at the McNair Campus
Houston, TX 77030-4202

 

MedicalResearch.com: What should readers take away from your study? 

  • First demonstration of an anti-α-synuclein antibody immunotherapy in patients with Parkinson’s Disease.
  • Robust target engagement led to mean reduction of up to 97% in serum free α-synuclein levels.
  • Central Nervous System penetration is supported by a dose-dependent increase in PRX002/RG7935 levels in Cerebral Spinal Fluid.
  • All dose levels of PRX002/RG7935 had acceptable safety and tolerability profiles, meeting the primary objective of this study
  • Data support ongoing PASADENA Phase 2 clinical study of PRX002/RG7935 (NCT03100149)  

Citation:

Jankovic J, Goodman I, Safirstein B, et al. Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti–α-Synuclein Monoclonal Antibody, in Patients With Parkinson DiseaseA Randomized Clinical TrialJAMA Neurol. Published online June 18, 2018. doi:10.1001/jamaneurol.2018.1487 

 

 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Gabapentin and Pregabalin Should Be Used Cautiously in Hemodialysis Patients

MedicalResearch.com Interview with:

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

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.  Continue reading

Guillain-Barré Syndrome With and Without Zika

MedicalResearch.com Interview with:

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

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.  Continue reading

Cannabidiol Reduced Drop Seizures in Severe Epilepsy Disorder

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.

Continue reading

Is Sickle Cell Really a Risk Factor for Stroke?

MedicalResearch.com Interview with :

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

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.

Continue reading

Link Between Epilepsy Drugs and Increased Risk of Dementia

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.  Continue reading

Epilepsy Patients Have Small Increased Risk of Unnatural Death

MedicalResearch.com Interview with:

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

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.  Continue reading

Genetic Overlap Between Some Types of ALS and and Dementia

MedicalResearch.com Interview with:

Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis

Dr. Karch

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.

Continue reading

Simple Screening Tool Predicts Parkinson’s Patients At Risk of Dementia

MedicalResearch.com Interview with:

Benjamin Dawson, B.Sc.  MD Candidate 2020

Benjamin Dawson

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. Continue reading

Duchenne Muscular Dystrophy: As Survival Increases, New Focus on Quality of Life

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.

Continue reading

Parkinson’s: Transcranial Stimulation of Motor and Cognitive Regions Reduced Gait Freezing

MedicalResearch.com Interview with:

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

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.

Continue reading

Oral vs IV Steroids for Acute Optic Neuritis

MedicalResearch.com Interview with:

Sarah A. Morrow MD, MS, FRCPC Associate Professor of Neurology Department of Clinical Neurological Sciences University of Western Ontario (Western)

Dr. Morrow

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.  Continue reading

Autoantibodies Generated By Zika Virus May Explain Some Consequences of Infection

MedicalResearch.com Interview with:

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

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.  Continue reading

BrainGate Technology Allows Tetraplegics To Rapidly Control Brain-Computer Interface

MedicalResearch.com Interview with:

Matthew McKee/BrainGate Collaboration

New technique enables rapid calibration of the BrainGate brain-computer interface.

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 (4×4 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.

Continue reading

Genetics Underlies Differences in Parkinson’s Disease Progression

MedicalResearch.com Interview with:

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

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).

Continue reading

First Steps in Elucidating How A Thought Becomes An Action

MedicalResearch.com Interview with:
Avgusta Shestyuk Senior researcher Helen Wills Neuroscience UC Berkeley

MedicalResearch.com Interview with:
Avgusta Shestyuk
Senior researcher
Helen Wills Neuroscience
UC Berkeley

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The paper describes neural activity that serves as a glue between perception and action, and that essentially reflects the process of thinking and deliberating about a particular problem and coming up with the response. This sustained activity is even present when we fail to generate a response but when we are still deliberating and thinking about it (that is we are not only tracking the process of response generation but the process of thinking about the response).

It is centered in the prefrontal cortex, which is known for higher order cortical processes, but it is also present in other brain regions, suggesting a distributed network of activity required for us to complete different tasks.

What is also unique about our study is that we were able to show that this type of activity is universal as it is present across multiple tasks of different complexity. This sustained stimulus-to-response activity is also multi-tasking – different local areas of the prefrontal cortex perform different operations in the stimulus-to-response window.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: This is the first step in trying to understand mechanisms of how we solve complex problems​.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Right now we are looking at the process, but future research will focus on how the prefrontal cortex coordinates distributed brain networks during the deliberation and whether we can decode the content of these thought processes (i.e., can we analyze this sustained brain activity and determine what action/behavior a person will perform next). This would be useful for brain-machine interface devices that help patients with various neurological problems such as stroke, locked-in syndrome, etc.

Disclosures:  Funded by:

National Science Foundation, NIH/National Institute of Mental Health, NIH/National Institute of Neurological Disorders and Stroke 

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Persistent neuronal activity in human prefrontal cortex links perception and action

Matar Haller, John Case, Nathan E. Crone, Edward F. Chang, David King-Stephens, Kenneth D. Laxer, Peter B. Weber, Josef Parvizi, Robert T. Knight & Avgusta Y. Shestyuk
Nature Human Behaviour2, 80–91 (2018)
doi:10.1038/s41562-017-0267-2
Published December 18 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

 

 

Multiple Sclerosis: Functional Changes After Inflammation May Partly Explain Clinico-Radiological Paradox

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.

Continue reading

Study Finds Modest Survival Increase in Parkinson’s Patients Who Receive Deep Brain Stimulation

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.

Continue reading

Tapeworm Drug May Be Repurposed To Fight Parkinson’s Disease

MedicalResearch.com Interview with:

Dr. Youcef Mehellou PhD Lecturer in Medicinal Chemistry Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University

Dr. Mehellou

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.

Continue reading