Science Current Events | Science News |

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

DNA repair factor linked to breast cancer may also play a role in Alzheimer's disease
Mutant forms of breast cancer factor 1 (BRCA1) are associated with breast and ovarian cancers but according to new findings, in the brain the normal BRCA1 gene product may also be linked to Alzheimer's disease.

Researchers grow retinal nerve cells in the lab
Johns Hopkins researchers have developed a method to efficiently turn human stem cells into retinal ganglion cells, the type of nerve cells located within the retina that transmit visual signals from the eye to the brain.

TGen and Barrow identify genes linked to stress-triggered heart disease
Researchers at the Translational Genomics Research Institute (TGen) and Barrow Neurological Institute have for the first time identified genetic risk factors that are linked to stress-induced cardiomyopathy (SIC), a rare type of heart disease.

DNA repair protein BRCA1 implicated in cognitive function and dementia
Researchers from the Gladstone Institutes have shown for the first time that the protein BRCA1 is required for normal learning and memory and is depleted by Alzheimer's disease.

Stem cell treatment mediates immune response to spinal cord injury in pre-clinical trials
When a blunt-force blow injures the spinal cord, the body's immune system can be both friend and foe. Sensing the injury, the immune system dispatches an inflammatory response composed of specialized cells called macrophages to dispose of dead tissue.

Neurogastronomy: How our brains perceive the flavor of food
Two women, seated at a table, told their stories in quiet tones. A group of chefs, some standing, others seated, leaned forward eagerly, clearly interested in what these two women had to say.

Batten disease may benefit from gene therapy
In a study of dogs, scientists showed that a new way to deliver replacement genes may be effective at slowing the development of childhood Batten disease, a rare and fatal neurological disorder.

Scientists ID genetic factors that influence body weight and neurological disorders
Many neurological disorders, such as Parkinson's disease and Alzheimer's disease, are marked by impaired motor skills.

Mindfulness meditation trumps placebo in pain reduction
Scientists at Wake Forest Baptist Medical Center have found new evidence that mindfulness meditation reduces pain more effectively than placebo.

Sleep interruptions worse for mood than overall reduced amount of sleep, study finds
A study led by Johns Hopkins Medicine researchers suggests that awakening several times throughout the night is more detrimental to people's positive moods than getting the same shortened amount of sleep without interruption.
More Neurological Disorders Current Events and Neurological Disorders News Articles

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...

Translational Neuroscience: Fundamental Approaches for Neurological Disorders

Translational Neuroscience: Fundamental Approaches for Neurological Disorders
by Mark H. Tuszynski (Editor)

Translational Neuroscience offers a far-reaching and insightful series of perspectives on the effort to bring potentially revolutionary new classes of therapies to the clinic, thereby transforming the treatment of human nervous system disorders. Great advances in the fields of basic neuroscience, molecular biology, genomics, gene therapy, cell therapy, stem cell biology, information technology, neuro devices, rehabilitation and others over the last 20 years have generated unprecedented opportunities to treat heretofore untreatable disorders of the nervous system. This book provides a wide-ranging yet detailed sample of many of these efforts, together with the methods for pursuing clinical translation and assessing clinical outcomes. Among the topics covered are Alzheimer’s disease,...

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? ...

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...

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...

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

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

Free Bonuses 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...

Immediate Early Genes in Sensory Processing, Cognitive Performance and Neurological Disorders

Immediate Early Genes in Sensory Processing, Cognitive Performance and Neurological Disorders
by Raphael Pinaud (Editor), Liisa A. Tremere (Editor)

This book provides a compilation of the most up-to-date literature on the topic of immediate early genes (IEGs). It reviews and details experiments and theories that challenge the reader to expand their view on how IEG research is currently being used to advance our understanding of static and active brain circuits. In addition, the book explores roles of IEGs in clinical neuropathology.

The Way to A: Empowering Children with Autism Spectrum and Other Neurological Disorders to Monitor and Replace Aggression and Tantrum Behavior

The Way to A: Empowering Children with Autism Spectrum and Other Neurological Disorders to Monitor and Replace Aggression and Tantrum Behavior
by Hunter Manasco (Author)

Children with ASD are often confused by our world of rules and consequences, including how their behavior impacts another person or situation. The result is often aggressive behavior. The Way to A, designed for children ages 3 to 9 years old, presents a simple, logical, and systematic strategy that clarifies and sequentially teaches the child how to manage his behavior by engaging in forethought and self-analysis before acting out. What sets this strategy apart is that it then goes on to give the child a personal and concrete incentive to use the alternative behavior. Developed with visual learners in mind, the book offers the ultimate in customization – the laminated pages may be written on and wiped clean as new situations come up. The illustrations are delightful and use the concrete...

Evidence-Based Neurology: Management of Neurological Disorders (Evidence-Based Medicine)

Evidence-Based Neurology: Management of Neurological Disorders (Evidence-Based Medicine)
by Bart Demaerschalk (Editor), Dean Wingerchuk (Editor), Livia Candelise (Editor)

From an expert editor team drawn from the Cochrane Neurological Network, Evidence-Based Neurology provides specialists and those in training with the skills and knowledge to apply evidence-based practice in the clinical setting.
fills the gap between guidelines and primary studies as well as between primary and secondary scientific medical literature summarizes the most recent and important findings on treatments for neurological patients measures the benefit and, when applicable, the risk of harm inherent in specific neurological interventions now includes new non-clinical topics of interest to neurologists such as education and research

Dear God Please Give Me MS: Fighting from the brink of death when you look just fine

Dear God Please Give Me MS: Fighting from the brink of death when you look just fine
by 2MCH4YA Publishing

"If you have never contemplated suicide because of a crippling medical condition, you will want to read this to recognize the hidden signs of a Registered Nurse who has!"

I’ve had this disease called multiple sclerosis (M.S.) since I was 18 and didn’t know it until the Fall of 2014, “literally and figuratively.” For a little over a year I’ve made adjustments to my life and learned to “LIVE” in spite of this crippling neurological disorder. Only a select few knew of my struggle. Only ONE knew what that actually consisted of. My wife of 26 years has been so instrumental in helping me to cope, and now I move forward with strength and faith renewed.

But, there was a solid month in 2014 when I struggled between “life and death” and this is the...

© 2015