The 'worm' holds the key to treating epilepsy—new possibilities for rapid drug discovery

September 26, 2016, Florida Atlantic University
Monica Risley, co-lead author and a Ph.D. student in FAU’s Integrative Biology and Neuroscience program, as well as a student in the new International Max Planck Research School in Brain and Behavior. Credit: Florida Atlantic University

Current methods to control epilepsy, which affects 1 in 26 Americans, are not only inefficient but haven't improved in more than 150 years when the first anticonvulsant drug was developed. Treatment options include invasive surgeries and a combination of antiepileptic drugs that surprisingly don't work in more than 30 percent of patients. Noninvasive treatments are limited for easing symptoms partially due to the complexity of the disorder and lack of knowledge of specific molecular malfunctions. In recent years, fewer and fewer drugs have been introduced into the market most likely due to exhausted screening techniques and less efficient methods for predicting drug effectiveness.

Researchers from Florida Atlantic University, in collaboration with The Scripps Research Institute, have opened up the possibilities for rapid drug screens to treat seizures in the near future by developing the smallest whole-animal electroconvulsive seizure model using a microscopic nematode worm. Electroshock is one of the most common experimental models of acute and chronic seizure in mammals to study epilepsy. The researchers have been able to demonstrate, that just like rodents and even fruit flies, the tiny 1 millimeter C.elegans worm also can undergo an electroconvulsive seizure.

The study, "Modulating Behavior in C.elegans Using Electroshock and Antiepileptic Drugs," just published in PLOS One, has led the researchers to build on the current animal models for inducing seizures via electroconvulsion in the genetically modifiable C.elegans that only has 302 brain cells called neurons. C.elegans has been used for decades as a model animal to study the genetic and molecular underpinnings of neurological disorders through a number of techniques including bio imaging, electrophysiology and behavior.

For the study, researchers treated the worms with several antiepileptic drugs approved for human use, which improved recovery from electroshock seizures worsened by genetic or pharmacological pro-convulsants.

"We were very excited to discover that when we used a typical genetic mutation that was more susceptible to electroconvulsive seizures, we were able to actually rescue these worms by treating them with FDA approved human antiepileptic drugs beforehand," said Monica Risley, co-lead author and a Ph.D. student in FAU's Integrative Biology and Neuroscience program, as well as a student in the new International Max Planck Research School in Brain and Behavior.

Because this new method is rapid, inexpensive and has shown relevance with existing antiepileptic drugs, the C.elegans electroshock assay developed at FAU has the potential to become an efficient screening tool for human seizure therapeutics.

"The fact that we can induce a short seizure, of approximately 1 to 3 minutes long, with the exact timing of an electrical pulse, and that these worms react well to , makes this new assay a perfect model for high-speed drug screens in multi-welled plate readers," said Ken Dawson-Scully, Ph.D., corresponding author and associate professor in the Department of Biological Sciences and associate director of the FAU Brain Institute.

Dawson-Scully notes that the ability to use C.elegans in high speed robotic drug testing facilities like those at Scripps Florida, will enable testing of hundreds of thousands of compounds, even in combinations, using this automated process. "The cost to run high throughput testing for antiepileptic drug candidates would cost a fraction in time and money compared to the experiments available today," said Dawson-Scully.

Explore further: Some psychotic disorders may be induced by drugs designed to combat effects of epilepsy

More information: Monica G. Risley et al. Modulating Behavior in C. elegans Using Electroshock and Antiepileptic Drugs, PLOS ONE (2016). DOI: 10.1371/journal.pone.0163786

Related Stories

Some psychotic disorders may be induced by drugs designed to combat effects of epilepsy

August 9, 2016
Today Brain publishes a new study indicating that antiepileptic drugs designed to reduce seizures, may also induce psychotic disorders in some patients.

Recommendations address how to manage seizures in infants

June 1, 2015
New recommendations offer insights on strategies for treating infants with seizures. In an Epilepsia report, child neurologists who are members of the International League Against Epilepsy note that intervening at the time ...

Scientists fish for new epilepsy model and reel in potential drug

September 3, 2013
According to new research on epilepsy, zebrafish have certainly earned their stripes. Results of a study in Nature Communications suggest that zebrafish carrying a specific mutation may help researchers discover treatments ...

Polypharamocological drugs in the treatment of epilepsy: The comprehensive review of marketed and new emerging molecules

July 13, 2016
The researchers in the laboratory of Dr. Manisha Tiwari have recently reviewed "Polypharamocological Drugs in the Treatment of Epilepsy: The Comprehensive Review of Marketed and New Emerging Molecules".

Folic acid during pregnancy could help to prevent autism caused by antiepileptic drugs

June 1, 2016
If pregnant women take antiepileptic drugs, the child can develop autistic traits. The administration of folic acid preparations appears to be a suitable means of preventing this serious side-effect. This finding is suggested ...

Treatments available for drug-resistant epilepsy

August 22, 2016
One in 26 people will develop epilepsy – a chronic disease characterized by unpredictable seizures—in their lifetime.

Recommended for you

Brain aging may begin earlier than expected

February 20, 2018
Physicists have devised a new method of investigating brain function, opening a new frontier in the diagnoses of neurodegenerative and ageing related diseases.

Brain immune system is key to recovery from motor neuron degeneration

February 20, 2018
The selective demise of motor neurons is the hallmark of Lou Gehrig's disease, also known as amyotrophic lateral sclerosis (ALS). Yet neurologists have suspected there are other types of brain cells involved in the progression ...

Every experience that the brain perceives is unique

February 20, 2018
Neuronal activity in the prefrontal cortex represents every experience as "novel." The neurons adapt their activity accordingly, even if the new experience is very similar to a previous one. That is the main finding of a ...

Electrical implant reduces 'invisible' symptoms of man's spinal cord injury

February 19, 2018
An experimental treatment that sends electrical currents through the spinal cord has improved "invisible" yet debilitating side effects for a B.C. man with a spinal cord injury.

Lab-grown human cerebellar cells yield clues to autism

February 16, 2018
Increasing evidence has linked autism spectrum disorder (ASD) with dysfunction of the brain's cerebellum, but the details have been unclear. In a new study, researchers at Boston Children's Hospital used stem cell technology ...

Fragile X syndrome neurons can be restored, study shows

February 16, 2018
Fragile X syndrome is the most frequent cause of intellectual disability in males, affecting one out of every 3,600 boys born. The syndrome can also cause autistic traits, such as social and communication deficits, as well ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.