Science Current Events | Science News | Brightsurf.com
 

Rare Disease in Amish Children Sheds Light on Common Neurological Disorders, Penn Study Shows

May 12, 2010

PHILADELPHIA - So often the rare informs the common. Penn researchers investigating a regulatory protein involved in a rare genetic disease have shown that it may be related to epileptic and autistic symptoms in other more common neurological disorders.

A team of researchers from the University of Pennsylvania School of Medicine, led by Peter B. Crino, MD, PhD, associate professor of Neurology and director of the Penn Epilepsy Center, demonstrate how mutations in the STRAD-alpha gene can cause a disease called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy) syndrome, found in a handful of Amish children. PMSE is characterized by an abnormally large brain, cognitive disability, and severe, treatment-resistant epilepsy.

Specifically, in an animal model, they found that the lack of the STRAD-alpha protein due to genetic mutations causes activation of the signaling pathway involving another protein called mTOR. In humans, this in turn may promote abnormal cell growth and cognitive problems in the developing brains of children. STRAD-alpha and mTOR proteins are part of a complex molecular network implicated in other, more common neurological disorders, many of which have autism-like symptoms as a component.

"The identification of a new gene that regulates mTOR provides fascinating insights into how mTOR pathway dysfunction may be associated with neurological disorders," says Crino. "Each new mTOR regulatory protein that is identified provides a new possible therapeutic target for drug development and treatment."

The research on PMSE - published this month in the Journal of Clinical Investigation - reveals clues about more common neurological disorders characterized by benign tumors and malformations of the brain, the most common of which is tuberous sclerosis complex (TSC). The root cause of TSC also lies in mutations in proteins along the mTOR pathway, however a different protein is affected compared to PMSE.

"It is quite compelling that TSC, a relatively common disorder, and PMSE, a rare disorder, are linked by a common cellular pathway, and exhibit similar severe neurological features," notes Crino. "In our study, we found that we could reverse some of the cellular features that result from STRAD-alpha deficiency in cell culture models of PMSE. This provides important conceptual support for more widespread treatment approaches that modify mTOR signaling in neurological disorders associated with epilepsy, autism, and cognitive disability."

Current estimates place tuberous sclerosis complex-affected births at one in 6,000. Nearly 1 million people worldwide are known to have TSC, with approximately 50,000 in the United States.

PMSE, on the other had, has only been described in 25 people in Lancaster County, PA. It's incidence among other Amish populations, let alone the rest of the country, is unknown. PMSE is also known as pretzel syndrome in the Amish community, because the lax joints of patients fold over easily. PMSE was identified in an Amish, or Old Order Mennonite pediatric population in 2007 by researchers from Penn and the Clinic for Special Children in Lancaster, PA, a genetic clinic devoted to the needs of the Amish.

The mTOR pathway normally controls cell growth, but in PMSE uncontrolled mTOR signaling leads to increases in brain size and areas in which the cerebral cortex is malformed. To prove this, the researchers knocked down the activity of the STRAD-alpha protein in a mouse model and caused malformations of the developing brain. The structure of these malformations was similar to what is seen in human PMSE and TSC and supports the conclusion that normal brain development in part depends on normal STRAD-alpha function. Localized brain malformations are among the most common causes of epilepsy and neurological disability in children.

This research was funded by the National Institute of Neurological Diseases and Stroke.

Ksenia Orlova, PhD, a graduate student in the Crino lab and Kevin Strauss, MD, Medical Director at the Clinic for Special Children, were also co-authors on the JCI paper.

Penn Medicine


Related Neurological Disorders Current Events and Neurological Disorders News Articles


The deadly toxin acrolein has a useful biological role
Scientists from RIKEN in Japan have discovered that acrolein--a toxic substance produced in cells during times of oxidative stress--in fact may play a role in preventing the process of fibrillation, an abnormal clumping of peptides that has been associated with Alzheimer's disease and other neural diseases.

New study surveys genetic changes linked with Parkinson's disease
After Alzheimer's, Parkinson's disease (PD) is the leading neurodegenerative disorder, affecting close to a million Americans, with 50,000 new cases diagnosed every year. A progressive disorder of the nervous system affecting movement, PD typically strikes adults in mid-life.

Avoiding mixtures of different mitochondria leads to effective mitochondrial replacement
Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute discovered an important biological phenomenon in human cells that will help scientists and clinicians design safer treatments to prevent mitochondrial diseases.

Lowering blood pressure reduces risk of heart disease in older adults
Intensive therapies to reduce high blood pressure can cut the risk of heart disease in older adults without increasing the risk for falls, according to doctors at Wake Forest Baptist Medical Center.

NIH-funded study reveals how differences in male and female brains emerge
Nematode worms may not be from Mars or Venus, but they do have sex-specific circuits in their brains that cause the males and females to act differently.

Breast cancer drug found to reduce seizures
A class of drug that inhibits estrogen production and is used to treat breast cancer has been found to quickly and effectively suppress dangerous brain seizures, according to a new Northwestern University study.

TGen and international team find new avenues of precision medicine for treating cancer
An international team of scientists, including those at the Translational Genomic Research Institute (TGen), have discovered new avenues of potential treatments for a rare and deadly cancer known as Adrenocortical Carcinoma, or ACC.

TGen-ASU researchers find tiny genetic switches in lizard tail regeneration
Any kid who pulls on a lizard tail knows it can drop off to avoid capture, but how they regrow a new tail remains a mystery.

Breast milk linked to significant early brain growth in preemies
Feeding premature babies mostly breast milk during the first month of life appears to spur more robust brain growth, compared with babies given little or no breast milk.

Researchers find possible treatment for suppressed immunity from spine injuries
Scientists report in Nature Neuroscience they have identified an underlying cause of dangerous immune suppression in people with high level spinal cord injuries and they propose a possible treatment.
More Neurological Disorders Current Events and Neurological Disorders News Articles

Disconnected Kids: The Groundbreaking Brain Balance Program for Children with Autism, ADHD, Dyslexia, and Other Neurological Disorders

Disconnected Kids: The Groundbreaking Brain Balance Program for Children with Autism, ADHD, Dyslexia, and Other Neurological Disorders
by Dr. Robert Melillo (Author)


The proven, drug-free program to treat the cause-not just the symptoms-of autism spectrum disorders and related conditions.

Each year, an estimated 1.5 million children-one out of every six-are diagnosed with autism, Asperger's syndrome, ADHD, dyslexia, and obsessive compulsive disorder. Dr. Robert Melillo brings a fundamentally new understanding to the cause of these conditions with his revolutionary Brain Balance Program(tm). It has achieved real, fully documented results that have dramatically improved the quality of life for children and their families in every aspect: behavioral, emotional, academic, and social. Disconnected Kids shows parents how to use this drug-free approach at home, including:Fully customizable exercises that target physical, sensory, and academic...

Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders

Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders
by Michael J. Zigmond (Editor), Joseph T. Coyle (Editor), Lewis P. Rowland (Editor)


Neurobiology of Brain Disorders is the first book directed primarily at basic scientists to offer a comprehensive overview of neurological and neuropsychiatric disease. This book links basic, translational, and clinical research, covering the genetic, developmental, molecular, and cellular mechanisms underlying all major categories of brain disorders. It offers students, postdoctoral fellows, and researchers in the diverse fields of neuroscience, neurobiology, neurology, and psychiatry the tools they need to obtain a basic background in the major neurological and psychiatric diseases, and to discern connections between basic research and these relevant clinical conditions. This book addresses developmental, autoimmune, central, and peripheral neurodegeneration; infectious diseases; and...

Autism: A Neurological Disorder of Early Brain Development

Autism: A Neurological Disorder of Early Brain Development
by Roberto Tuchman (Editor), Isabelle Rapin (Editor)


Written by child neurologists, this comprehensive, multi-authored volume on autism systematically discusses the classification, epidemiology and neurobiology of autism. Autism lacks a unique etiology or specific pathology, so the behaviorally defined social deficits, language impairments and repetitive behaviors that define autism are explored from a developmental neurology perspective. The evidence suggesting that autism is a disorder of neuronal development is reviewed by experts on the genetics, neuroanatomy and neuroradiology, neurochemistry, immunology, and neurophysiology of autism. Chapters provide comprehensive reviews of the common neurological problems associated with autism such as epilepsy, sleep disturbances and motor and sensory deficits. Neuropsychological assessment,...

Gut microbiota, gluten and even more - the role of eosinophil cationic protein in neurological disorders: The author's conjecture: increase in ECP contributes to cerebral vascular spasms

Gut microbiota, gluten and even more - the role of eosinophil cationic protein in neurological disorders: The author's conjecture: increase in ECP contributes to cerebral vascular spasms


In a nutshell: an increased level of eosinophil cationic protein contributes to cerebral vascular spasms. The material was prepared by a person without medical education after struggling with neurological disorders described in the article. The intended audience is professionals in neurology, neurobiology, gastroenterology and other medical disciplines. Ideas stated in the essay need to be validated.

There may be some loss in translation, so if any question arise, please contact the author via e-mail mbrain16@outlook.com.

Length: 22 pages (Amazon's estimation).
-----------------------------------------

ABSTRACT

Various cerebrovascular diseases and concomitant neurological disorders may be connected with an increased level of eosinophil...

Neurological Disorders in Famous Artists - Part 3 (Frontiers of Neurology and Neuroscience)

Neurological Disorders in Famous Artists - Part 3 (Frontiers of Neurology and Neuroscience)
by S. Karger


The third part of Neurological Disorders in Famous Artists presents painters, musicians, and writers who had to fight against an acute or chronic neurological disease. Sometimes this fight was without success (e.g. Shostakovich, Schumann, Wolf, Pascal), but often a dynamic and paradoxical creativity of the clinical disorder was integrated into their artistic production (e.g. Klee, Ramuz). Occasionally, some even wrote the first report of a medical condition they observed in themselves, like Stendhal who made a detailed report of aphasic transient ischemic attacks before dying of stroke shortly thereafter. In rarer instances, a neurological disease was inaccurately attributed to an artist in order to explain certain features of his work (de Chirico, Schiele). Some chapters in this...

Does Stress Damage the Brain?: Understanding Trauma-Related Disorders from a Mind-Body Perspective

Does Stress Damage the Brain?: Understanding Trauma-Related Disorders from a Mind-Body Perspective
by J. Douglas Bremner M.D. (Author)


Everyone who has ever experienced stress, or wondered about the effects of stress on their minds and bodies, will benefit from the insights in this clearly written and accessible book.
Why is it that we can remember exactly where we were when John Kennedy was shot, or when the Space Shuttle Challenger exploded, or on September 11, 2001? Does what we see, hear, feel, and in other ways experience, especially during times of stress, result in permanent changes to our brains? Is this one of the reasons stressful events become seared in our memories? These provocative questions, and many others, are answered here by J. Douglas Bremner, a leading scientist whose discoveries, and that of his colleagues, showed that extreme stress may result in lasting damage to the brain, especially a part...

Disorders of Movement: A Guide to Diagnosis and Treatment

Disorders of Movement: A Guide to Diagnosis and Treatment
by Davide Martino (Author), Alberto J. Espay (Author), Alfonso Fasano (Author), Francesca Morgante (Author)


This concise but comprehensive book will help interested readers in the health care professions to navigate their way through the jungle of movement disorders, including the potentially complex differential diagnosis and management. The different disorders are discussed in individual sections that explain how to examine the patient and recognize the disorder from its basic phenomenology, how to confirm a diagnosis, how to distinguish a particular disorder from related conditions, and how to treat each disorder effectively. The book makes liberal use of diagrams, algorithms, tables, summary boxes, and illustrations to facilitate solution of clinical problems at the bedside and to solidify previously learned clinical and therapeutic concepts. It will be of interest to a broad audience of...

NCLEX: Neurological Disorders: Easily Dominate The Test With 105 Practice Questions & Rationales to Help You Become a Nurse! (Nursing Review Questions ... Guide, Science, Medical Career Book 14)

NCLEX: Neurological Disorders: Easily Dominate The Test With 105 Practice Questions & Rationales to Help You Become a Nurse! (Nursing Review Questions ... Guide, Science, Medical Career Book 14)
by Nurse Superhero


FREE BONUS BOOK INCLUDED
Don't have a kindle? No worries! You can easily read this book through the Kindle Cloud Reader on your Computer, Smart Phone, iPad, iPhone, or you can download the Kindle App to almost any device.

105 Practice Questions + Limited Time Free Bonus Inside = The Fear Of Failure Eliminated Forever!
In 1 hours or less you will have the skills to absolutely crush the Neurological questions of the NCLEX!

Upon downloading this book you will receive an additional *FREE Bonus Ebook Inside*

NCLEX SUCCESS: What You Need To Easily Crush The NCLEX On The First Try

You Will Love The Free Bonus Ebook Because...
I have found exactly how to approach each question and saved you 100's of hours. You can ALSO use this free...

Gene Therapy for Neurological Disorders: Methods and Protocols (Methods in Molecular Biology)

Gene Therapy for Neurological Disorders: Methods and Protocols (Methods in Molecular Biology)
by Fredric P. Manfredsson (Editor)


This volume provides a clear and detailed roadmap of how to design and execute a gene therapy experiment in order to obtain consistent results. Chapters in this book disseminate bits of unknown information that are important to consider during the course of experimentation and will answer questions such as: What delivery vehicle do you use?; How will you ensure that your vector retains stability?; What expression system best fits your needs?; What route will you choose to deliver your gene therapy agent?; How will you model the neurodegenerative disorder that you aim to investigate and what are the proven methods to treat these disorders in preclinical models? Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective...

Neuropsychological Neurology: The Neurocognitive Impairments of Neurological Disorders

Neuropsychological Neurology: The Neurocognitive Impairments of Neurological Disorders
by A. J. Larner (Author)


Understanding the cognitive aspects of neurological disorders is essential to manage effectively patients suffering from these conditions. This book begins by outlining the various cognitive domains and how these can be tested, before covering in depth the cognitive deficits seen in prototypical neurodegenerative cognitive disorders, (Alzheimer's disease, frontotemporal dementias, Huntington's disease, prionoses), and other common neurological disorders that may be complicated by cognitive impairment (stroke, multiple sclerosis, Parkinson's disease, brain tumours). This Second Edition has been completely revised and updated, with new material added throughout, including two new chapters: Sleep-Related Disorders, and Psychiatric Disorders in the Cognitive Function Clinic. This an...

© 2017 BrightSurf.com