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


Stanford researchers compare mammals' genomes to aid human clinical research
For years, scientists have considered the laboratory mouse one of the best models for researching disease in humans because of the genetic similarity between the two mammals.

New insights that link Fragile X syndrome and autism spectrum disorders
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability (ID), as well as the most frequent monogenic cause of autism spectrum disorders (ASD).

New Alzheimer's-related memory disorder identified
A multi-institutional study has defined and established criteria for a new neurological disease closely resembling Alzheimer's disease called primary age-related tauopathy (PART).

Multiple models reveal new genetic links in autism
With the help of mouse models, induced pluripotent stem cells (iPSCs) and the "tooth fairy," researchers at the University of California, San Diego School of Medicine have implicated a new gene in idiopathic or non-syndromic autism.

Otago neuroscientists reveal mechanism crucial to molding male brains
University of Otago researchers have discovered that neural circuitry they previously showed was vital to triggering ovulation and maintaining fertility also plays a key role in moulding the male brain.

The cat's meow: Genome reveals clues to domestication
Cats and humans have shared the same households for at least 9,000 years, but we still know very little about how our feline friends became domesticated. An analysis of the cat genome by researchers at Washington University School of Medicine in St. Louis reveals some surprising clues.

Multiple models reveal new genetic links in autism
With the help of mouse models, induced pluripotent stem cells (iPSCs) and the "tooth fairy," researchers at the University of California, San Diego School of Medicine have implicated a new gene in idiopathic or non-syndromic autism.

Overall risk of birth defects appears low for women taking antiretrovirals during early pregnancy
Among pregnant women infected with HIV, the use of antiretroviral (ARV) medications early in pregnancy to treat their HIV or to prevent mother-to-child transmission of HIV does not appear to increase the risk of birth defects in their infants.

Scientists create Parkinson's disease in a dish
A team of scientists led by The New York Stem Cell Foundation (NYSCF) Research Institute successfully created a human stem cell disease model of Parkinson's disease in a dish.

Getting to the heart of the heart
For years, a multidisciplinary team of Johns Hopkins researchers has tracked an elusive creature, a complex of proteins thought to be at fault in some cases of sudden cardiac death.
More Neurological Disorders Current Events and Neurological Disorders News Articles

Amazing Brain - Neurological Disorders

Amazing Brain - Neurological Disorders
by Connie Goldsmith (Author)


The Amazing Brain series offers exciting answers about how our brain works and why we respond to the world the way we do. Questions addressed in this 4-vol. set include: Do male and female brains work differently? Can music enhance learning and boost brain development? Was Einstein's brain more unique than the average brain? What dependencies are really true addictions? Can brain cells regenerate? ...

Biomarkers of Brain Injury and Neurological Disorders

Biomarkers of Brain Injury and Neurological Disorders
by Kevin K. W. Wang (Editor), Zhiqun Zhang (Editor), Firas H. Kobeissy (Editor)


This book explores the recent advances in the techniques and platforms used in biomarker research that have revolutionized the way we study, diagnose, and treat brain injury conditions. The contributors describe different biomarker studies pertaining to brain injury and other neurological disorders and analyze the different models and technologies used to identify these biological markers. The book includes findings from "Omics research" that have been utilized to decipher and identify such biomarkers. It discusses protein, microRNA, and altered gene profiles and reviews neurological disorders such as multiple sclerosis, Charcot-Marie-Tooth disease, and prion and Alzheimer’s disease.

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...

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...

Understanding Equine Neurological Disorders: Your Guide to Horse Health Care and Management (Horse Health Care Library)

Understanding Equine Neurological Disorders: Your Guide to Horse Health Care and Management (Horse Health Care Library)
by Bradford G Bentz (Author), David E Granstrom (Foreword)


This book provides horse owners with the information they need to better comprehend the various neurological disorders and diseases that can afflict horses.

Driven to Distraction (Revised): Recognizing and Coping with Attention Deficit Disorder

Driven to Distraction (Revised): Recognizing and Coping with Attention Deficit Disorder
by Edward M. Hallowell M.D. (Author), John J. Ratey M.D. (Author)


Groundbreaking and comprehensive, Driven to Distraction has been a lifeline to the approximately eighteen million Americans who are thought to have ADHD. Now the bestselling book is revised and updated with current medical information for a new generation searching for answers.
 
Through vivid stories and case histories of patients—both adults and children—Hallowell and Ratey explore the varied forms ADHD takes, from hyperactivity to daydreaming. They dispel common myths, offer helpful coping tools, and give a thorough accounting of all treatment options as well as tips for dealing with a diagnosed child, partner, or family member. But most importantly, they focus on the positives that can come with this “disorder”—including high energy, intuitiveness, creativity, and...

Neurological Disorders due to Systemic Disease

Neurological Disorders due to Systemic Disease
by Steven L. Lewis (Editor)


Edited by Steven L Lewis, MD, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA How do you identify which neurologic syndromes occur due to systemic disease? Neurological problems commonly occur in the context of underlying systemic disease, and may even be the presenting symptom of a medical condition that has not yet been diagnosed. Consequently neurologists need to be aware when a neurological presentation might indicate an underlying systemic disorder. Neurologic al Disorders due to Systemic Disease provides the tools you need to make these connections. The unique neurologic presentation-based approach relates to the common clinical situations you encounter, including: Headache Stroke Movement disorders Neuromuscular disorders ...

The Everything Parent's Guide To Sensory Processing Disorder: The Information and Treatment Options You Need to Help Your Child with SPD

The Everything Parent's Guide To Sensory Processing Disorder: The Information and Treatment Options You Need to Help Your Child with SPD
by Terri Mauro (Author), Jenny L. Clark (Contributor)


If your child has been diagnosed with sensory processing disorder (SPD), you understand how simple, everyday tasks can become a struggle. With The Everything Parent's Guide to Sensory Processing Disorder, you can help your child learn how to reduce stress and minimize the symptoms of SPD. In this all-in-one guide, Terri Mauro provides all the information you need regarding SPD, including:An in-depth definition of SPD and its effects.The newest treatments, therapies, and diets.Techniques for use outside of the therapist's office.The latest research on physical causes of SPD.Advice for coping at school, home, and play. Your child deserves to live a life free of the difficulties SPD can bring. The Everything Parent's Guide to Sensory Processing Disorder gives you professional advice to help...

Scattered: How Attention Deficit Disorder Originates and What You Can Do About It

Scattered: How Attention Deficit Disorder Originates and What You Can Do About It
by Gabor Mate (Author)


Attention Deficit Disorder (ADD) has quickly become a controversial topic in recent years. Whereas other books on the subject describe the condition as inherited, Dr. Gabor Maté believes that our social and emotional environments play a key role in both the cause of and cure for this condition. In Scattered, he describes the painful realities of ADD and its effect on children as well as on career and social paths in adults. While acknowledging that genetics may indeed play a part in predisposing a person toward ADD, Dr. Maté moves beyond that to focus on the things we can control: changes in environment, family dynamics, and parenting choices. He draws heavily on his own experience with the disorder, as both an ADD sufferer and the parent of three diagnosed children. Providing a...

Hyperbaric Oxygen for Neurological Disorders

Hyperbaric Oxygen for Neurological Disorders
by John H. Zhang Md PhD - Editor (Author)


This timely textbook is the first ever to be published on hyperbaric oxygen and its potential applications in neurological diseases. The stellar list of 37 national and international contributors is more than impressive.
FROM THE EDITOR:
Hyperbaric oxygen (HBO) has been used as a therapeutic or an alternative therapeutic strategy for neurological diseases for many years. However, for most neurological diseases, HBO is being used without FDA and UHMS approval and therefore HBO is used to treat neurological diseases in mostly free-standing clinics. One of the key issues that has prevented HBO becoming part of mainstream medicine for neurological diseases is the lack of scientific evidence to support a possible neuroprotective effect of HBO. That is the reason for publishing this...

© 2014 BrightSurf.com