Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutations taking place only in the brain identified as the cause of intractable epilepsy

24.03.2015

KAIST researchers have discovered that brain somatic mutations in the MTOR gene induce intractable epilepsy and suggest a precision medicine to treat epileptic seizures.

Epilepsy is a brain disorder that afflicts more than 50 million people worldwide. Many epilepsy patients can control their symptoms through medication, but about 30% suffer from intractable epilepsy and are unable to manage the disease with drugs.


A schematic image shows how to detect brain specific mutations using next-generation sequencing technology with blood-brain paired samples. Simple comparison of non-overlapping mutations between affected and unaffected tissues is able to detect brain specific mutations. Copyright: KAIST

Intractable epilepsy causes multiple seizures, permanent mental, physical, and developmental disabilities, and even death. Therefore, surgical removal of the affected area from the brain has been used as a treatment for patients with medically refractory seizures, but this too fails to provide a complete solution because only 60% of the patients who undergo surgery are rendered free of seizures.

A Korean research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering at the Korea Advanced Institute of Science and Technology (KAIST) and Professor Dong-Seok Kim of the Epilepsy Research Center at Yonsei University College of Medicine has recently identified brain somatic mutations in the gene of mechanistic target of rapamycin (MTOR) as the cause of focal cortical dysplasia type II (FCDII), one of the most important and common inducers to intractable epilepsy, particularly in children.

They propose a targeted therapy to lessen epileptic seizures by suppressing the activation of mTOR kinase, a signaling protein in the brain. Their research results were published online in Nature Medicine on March 23, 2015.

FCDII contributes to abnormal developments of the cerebral cortex, ranging from cortical disruption to severe forms of cortical dyslamination, balloon cells, and dysplastic neurons. The research team studied 77 FCDII patients with intractable epilepsy who had received surgery to remove the affected regions from the brain. The researchers used various deep sequencing technologies to conduct comparative DNA analysis of the samples obtained from the patients’ saliva or brain and blood. They reported that about 16% of the studied patients had somatic mutations in their brain. Such mutations, however, did not take place in their blood or saliva DNA.

Professor Jeong Ho Lee of KAIST said, “This is an important finding. Unlike our previous belief that genetic mutations causing intractable epilepsy exist anywhere in the human body including the blood, specific gene mutations incurred only in the brain can lead to intractable epilepsy. From our animal model, we could see how a small fraction of mutations carrying neurons in the brain could affect its entire function.”

The research team recapitulated the pathogenesis of intractable epilepsy by inducing the focal cortical expression of mutated mTOR in the mouse brain via an electroporation method and observed as the mouse developed epileptic symptoms. They then treated these mice with a drug called “rapamycin” to inhibit the activity of mTOR protein and observed that it suppressed the development of epileptic seizures with cytomegalic neurons.

“Our study offers the first evidence that brain-somatic-activating mutations in MTOR cause FCDII, and we identified mTOR as a treatment target for intractable epilepsy,” said co-author Dr. Dong-Seok Kim, a neurosurgeon at Yonsei Medical Center with the most surgical experiences in treating patients with this condition.

The research paper is entitled “Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy.” (Digital Object Identifier #: 10.1038/nm.3824)

For further information contact:
Lan Yoon
Korea Advanced Institute of Science and Technology (KAIST)
Tel. +82-42-350-2294, +82-10-2539-4303 (cell phone)
hlyoon@kaist.ac.kr
www.kaist.edu

Lan Yoon | ResearchSEA
Further information:
http://www.researchsea.com

Further reports about: KAIST dysplasia epileptic epileptic seizures mTOR mutations neurons surgery

More articles from Health and Medicine:

nachricht The cytoskeleton of neurons has been found to be involved in Alzheimer's disease
18.01.2019 | University of the Basque Country

nachricht Bioinspired nanoscale drug delivery method developed by WSU, PNNL researchers
10.01.2019 | Washington State University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

Im Focus: Elucidating the Atomic Mechanism of Superlubricity

The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.

One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Additive manufacturing reflects fundamental metallurgical principles to create materials

18.01.2019 | Materials Sciences

How molecules teeter in a laser field

18.01.2019 | Life Sciences

The cytoskeleton of neurons has been found to be involved in Alzheimer's disease

18.01.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>