Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Potential Drug Discovered for Severe Form of Epilepsy

Published: Thursday, September 05, 2013
Last Updated: Thursday, September 05, 2013
Bookmark and Share
UCSF study found effectiveness of antihistamine on zebrafish bred to mimic disease.

An antihistamine discovered in the 1950s to treat itching may also prevent seizures in an intractable form of childhood epilepsy, according to researchers at UC San Francisco who tested it in zebrafish bred to mimic the disease.

The researchers said their unexpected discovery offers a glimmer of hope for families of children with Dravet Syndrome, a rare genetic disorder that manifests in early childhood with disabling, lifelong consequences. These include dozens, if not hundreds, of daily seizures, as well as profound cognitive and social deficits.

“It is very unfortunate for these children and families, as they often live from seizure to seizure,” said Scott C. Baraban, PhD, lead author of the article, UCSF William K. Bowes Jr. Endowed Chair in Neuroscience Research and professor of Neurological Surgery.

Small, translucent and easy to breed, zebrafish are increasingly being used in place of rodents to screen drugs for rare genetic disorders. But no one had used them for epilepsy drug screening until Baraban’s team found zebrafish with a genetic mutation identical to the one that causes Dravet Syndrome.

Baraban said his method of drug discovery could be used to screen drugs for any form of epilepsy caused by mutations in a single gene – a number of which were recently discovered in another UCSF study on epilepsy.

Drug Therapy for Genetic Forms of Epilepsy

Dravet Syndrome usually develops because of mutations in the SCN1A gene, which codes for proteins in sodium ion channels. These channels act as pores that allow charged ions to pass through the membranes of neurons and regulate how they fire. In Dravet Syndrome, these channels let in too many ions and the neurons fire excessively, causing seizures. Other forms of genetically-caused epilepsy involve similar problems in potassium and calcium channels.

While some adult forms of epilepsy can be treated by surgically removing small areas of electrically malfunctioning brain tissue, genetic forms of epilepsy cannot, because they involve neurons all over the brain. Instead, researchers are focusing their efforts on finding effective drugs.

Baraban’s team discovered the efficacy of clemizole, which had previously been used only as an antihistamine and an antiviral drug, by accident.

Since antihistamines can make seizures worse, it’s unlikely he would have focused on the drug if he hadn’t used a study design intended to circumvent bias about which drugs might work. Instead of beginning with a hypothesis based on previous findings, Baraban used a random assortment of 320 compounds in a chemical library of drugs that had already been approved by the Food and Drug Administration. He did not look to see what the drugs were until after he had his results.

Why clemizole works is still a mystery. Baraban’s group tried 10 other antihistamines, four mentioned in the paper and six others since then, and none blocked seizures. Baraban concluded that the antihistamine itself was probably not the mechanism of the drug’s anti-seizure effect and plans future studies to try to figure this out.

Using Zebrafish to Study Dravet Syndrome

This study used mutant zebrafish discovered a few years ago by then-UCSF neuroscientist, Herwig Baier, PhD, now at the Max Planck Institute of Neurobiology in Germany. By chance, one strain of the fish had a mutation in the same sodium channel gene as the one implicated in Dravet Syndrome.

Just like people with Dravet Syndrome, the fish with this mutation had spontaneous seizures that did not respond to many drugs used to treat epilepsy. But they did respond to a form of the ketogenic – or high-fat – diet, which also often helps reduce seizures in children with Dravet Syndrome.

The mutant fish also showed the same developmental pattern as children, whose seizures do not begin until after their first year. In fish, seizures began three days after fertilization. The fish typically died at 10 or 12 days. People with Dravet Syndrome are also vulnerable to sudden unexpected death in epilepsy, or SUDEP.

In these studies, Baraban and colleagues worked with larvae no larger than a human eyelash. They measured their brain activity with a micro-electrode just 1 micron in diameter and tracked their tiny, convulsive movements with special software. He said the seizures in these mutant fish closely resembled those in humans with Dravet Syndrome. Since the larvae are so small and easy to work with, they can screen five times as many drugs in his small laboratory as a much larger lab can do with rodents.

Baraban said that it’s important to use whole animals in screening drugs for epilepsy, since it arises from the activity of neural circuits containing many thousands of cells. Even so, his team plans to conduct lab studies to test clemizole’s effect on individual neurons generated from patients with Dravet Syndrome. They’ll use induced pluripotent stem cell (iPSC) technology, which involves generating individual neurons from patients with Dravet syndrome, as a preliminary step before testing the drug in people.

Baraban is a member of the Eli & Edythe Broad Center of Regeneration Medicine and Stem Cell Research. Other authors of the article, “Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment,” include senior staff research associate Matthew T. Dinday, BA, and Gabriela A. Hortopan, PhD, a postdoctoral fellow.Both work in Baraban’s Epilepsy Research Laboratory.

The research was funded by an Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) grant from the National Institute of Neurological Disorders and Stroke, the Dravet Syndrome Foundation and Citizens United for Research in Epilepsy.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Simple Technology Makes CRISPR Gene Editing Cheaper
University of California, Berkeley, researchers have discovered a much cheaper and easier way to target a hot new gene editing tool, CRISPR-Cas9, to cut or label DNA.
Friday, July 24, 2015
Printed "Smart Cap" Detects Spoiled Food
It might not be long before consumers can just hit “print” to create an electronic circuit or wireless sensor in the comfort of their homes.
Tuesday, July 21, 2015
Growing Spinal Disc Tissue
Scientists develop new method for growing spinal disc tissue in the lab for combating chronic back pain.
Friday, July 03, 2015
Delivering Drugs to the Right Place
Thomas Weimbs has developed a targeted drug delivery method that could potentially slow the progression of polycystic kidney disease.
Monday, June 29, 2015
The Deep Carbon Cycle
Over billions of years, the total carbon content of the outer part of the Earth—in its upper mantle, crust, oceans and atmospheres—has gradually increased, scientists report.
Tuesday, June 23, 2015
Designing New Pain Relief Drugs
Researchers have identified the molecular interactions that allow capsaicin to activate the body’s primary receptor for sensing heat and pain, paving the way for the design of more selective and effective drugs to relieve pain.
Thursday, June 11, 2015
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 2015
Genetic Markers for Detecting and Treating Ovarian Cancer
Custom bioinformatics algorithm identifies human mRNAs that distinguish ovarian cancer cells from normal cells and provide new therapeutic targets
Wednesday, May 27, 2015
Researchers Reverse Bacterial Resistance to Antibiotics
Evidence continues to surface that supports the premise that antibiotics which have been out of use could still be effective in treating drug-resistant bacteria.
Friday, May 08, 2015
Industry-Sponsored Academic Inventions Spur Increased Innovation
Analysis questions assumption that corporate support skews science toward inventions that are less useful than those funded by the government or non-profit organizations.
Monday, March 24, 2014
May the Cellular Force be With You
Like tiny construction workers, cells sculpt embryonic tissues and organs in 3D space.
Friday, December 13, 2013
Grant Supports Creation of Patient-Derived Stem Cell Lines
Researchers have received a two-year, $600,000 grant from the National Institute on Aging to develop and study patient-derived stem cell lines.
Thursday, December 12, 2013
Prostate Cancer Stem Cells are a Moving Target
Researchers have discovered how prostate cancer stem cells evolve as the disease progresses, a finding that could help point the way to more highly targeted therapies.
Friday, December 06, 2013
International Fruit Pest Targeted by Genomic Research
The spotted wing drosophila is itself being targeted, thanks to groundbreaking genome sequencing.
Friday, December 06, 2013
Scientific News
Study Finds Brain Chemicals that Keep Wakefulness in Check
Researchers to develop new drugs that promote better sleep, or control hyperactivity in people with mania.
Sorting Through Cellular Statistics
Aaron Dinner, professor in chemistry, and his graduate student Herman Gudjonson are trying to read the manual of life, DNA, as part of the Dinner group’s research into bioinformatics—the application of statistics to biological research.
Playing 'Tag' with Pollution lets Scientists See Who's It
Using a climate model that can tag sources of soot from different global regions and can track where it lands on the Tibetan Plateau, researchers have determined which areas around the plateau contribute the most soot — and where.
Women’s Immune System Genes Operate Differently from Men’s
A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
First Artificial Ribosome Designed
Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell.
High-Resolution 3D Images Reveal the Muscle Mitochondrial Power Grid
NIH mouse study overturns scientific ideas on energy distribution in muscle.
Expanding the Brain
A team of researchers has identified more than 40 new “imprinted” genes, in which either the maternal or paternal copy of a gene is expressed while the other is silenced.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Study Uncovers Target for Preventing Huntington’s Disease
Scientists from Cardiff University believe that a treatment to prevent or delay the symptoms of Huntington’s disease could now be much closer, following a major breakthrough.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!