Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New treatments for epilepsy, behavioral disorders could result from Wayne State studies

12.10.2012
Three studies conducted as part of Wayne State University's Systems Biology of Epilepsy Project (SBEP) could result in new types of treatment for the disease and, as a bonus, for behavioral disorders as well.

The SBEP started out with funds from the President's Research Enhancement Fund and spanned neurology, neuroscience, genetics and computational biology. It since has been supported by multiple National Institutes of Health-funded grants aimed at identifying the underlying causes of epilepsy, and it is uniquely integrated within the Comprehensive Epilepsy Program at the Wayne State School of Medicine and the Detroit Medical Center.

Under the guidance of Jeffrey Loeb, M.D., Ph.D., associate director of the Center for Molecular Medicine and Genetics (CMMG) and professor of neurology, the project brings together researchers from different fields to create an interdisciplinary research program that targets the complex disease. The multifaceted program at Wayne State is like no other in the world, officials say, with two primary goals: improving clinical care and creating novel strategies for diagnosis and treatment of patients with epilepsy.

The three studies were published in high-impact journals and use human brain tissue research to identify new targets for drug development, generate a new animal model and identify a new class of drugs to treat the disease. In the first study, "Layer-Specific CREB Target Gene Induction in Human Neocortical Epilepsy," published recently in the Journal of Neuroscience, donated human brain samples were probed to identify 137 genes strongly associated with epileptic seizures.

Researchers then showed that the most common pathway is activated in very specific layers of the cortex, and that it's associated with increased numbers of synapses in those areas. Because epilepsy is a disease of abnormal neuronal synchrony, the finding could explain why some brain regions produce clinical seizures.

"Higher density of synapses may explain how abnormal epileptic discharges, or spikes, are formed, and in what layer," Loeb said, adding that localizing the exact layer of the brain in which that process occurs is useful both for understanding the mechanism and for developing therapeutics.

The first study, which identified a new drug target for epilepsy, precipitated a second study that has found such a drug.

In the second study, "Electrical, Molecular and Behavioral Effects of Interictal Spiking in the Rat," published recently in Neurobiology of Disease, SBEP researchers found that the same brain layers in the rat are activated as in the human tissues and searched for a drug to target those layers. In fact, the first drug they tried, a compound called SL327 that has been used in nonhuman subjects to understand how memory works, "worked like a dream," Loeb said. "SL327 prevented spiking in rat brains," he said, "which not only prevented seizures, but led to more normal behaviors as well."

That finding led to collaborations between Loeb's lab and Nash Boutros, M.D., professor of psychiatry and behavioral neurosciences, and the Belgian drug company UCB.

"Whereas animals that developed epileptic spiking became hyperactive, those treated with the drug and had less spiking in their brains were more like normal animals," Loeb said. "Now whenever we screen for drugs for epilepsy, we look at behavior as well as epileptic activity."

Noting that many seizure medicines currently are used to treat various psychiatric disorders, Loeb said the SBEP team's latest round of work marks a "nice crossover" between psychiatry and neurology in the field of drugs related to epilepsy.

In the third study, just published in Genetics, researchers say they have found "fascinating interrelationships" between "junk" long noncoding RNA and normal RNA that are regulated by human brain activity. That work has the potential to be translated into new genetic treatments for epilepsy.

"This study shows how the human brain deals with half of the human genome in its most important function, electrical activity, using human brain tissue from patients with epilepsy to understand the basic molecular processes of how the brain works, and what's unique about human brains compared to the brains of less-developed species," Loeb said.

The third study, titled "Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks," is a collaborative effort between Loeb's lab and Leonard Lipovich, Ph.D., assistant professor of neurology and molecular medicine and genetics. It found that certain genes and their noncoding counterparts (which some researchers have called "junk") are co-regulated, or turned on at the same time, with brain activity.

"This tells us that some of these noncoding genes may actually have functions in brain activity," Loeb said. "In some, turning one on turns another one off. Some are regulatory and can be used to control plasticity genes — which are involved in memory, learning and behavior — with one of these novel, noncoding RNA genes."

The synergy exhibited by the three studies, Loeb said, is testimony to the multidisciplinary nature of Wayne State's systems biology platform, partly developed with a remarkable three-dimensional database created in cooperation with Farshad Fotouhi, Ph.D., dean of the College of Engineering, and Jing Hua, Ph.D., associate professor of computer science.

"SBEP is a cross-campus endeavor," Loeb said. "These studies are the fruits of the labor of this consortium and only exist at WSU. The next steps will be translating these exciting findings into new treatments to prevent or even cure patients with epilepsy and other psychiatric disorders."

The above studies were funded by the National Institute of Neurological Diseases and Stroke of the National Institutes of Health (NIH), grant Nos. R01NS045207, R01Ns05058802, F30NS049776; by the National Institute on Drug Abuse of the NIH, grant No. 1R03DA0262-01; and by the State of Michigan Joe Young Funds to the Department of Psychiatry and Behavioral Neurosciences, and were started with help from the WSU President's Research Enhancement Fund.

Wayne State University is one of the nation's pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit http://www.research.wayne.edu.

Julie O'Connor | EurekAlert!
Further information:
http://www.wayne.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>