Navigation Links
Scripps research study opens the door to new class of drugs for epileptic seizures
Date:7/29/2010

LA JOLLA, CA July 28, 2010 For Immediate Release A chemical compound that boosts the action of a molecule normally produced in the brain may provide the starting point for a new line of therapies for the treatment of epileptic seizures, according to a new study by scientists at The Scripps Research Institute.

"This compound really provides a new angle for developing drugs to treat seizures," says Scripps Research Assistant Professor Xiaoying Lu, who co-authored the paper with Professor Edward Roberts, Chair of the Molecular and Integrative Neurosciences Department Tamas Bartfai, and colleagues.

As described this week in Proceedings of the National Academy of Sciences (PNAS), the new compound effectively reduced the frequency and severity of seizures in mice and rats.

About 50 million people worldwide are affected by epilepsy, a disease characterized by recurrent, unprovoked seizures. As a result of the seizures, people may have violent muscle spasms or lose consciousness and, in some cases, suffer from brain damage or die. Epileptic seizures are caused by the rapid and excessive firing of a population of neurons in an area of the brain known as the cortex. The dozen-plus medicines currently on the market to treat epilepsy work to reduce this excessive firing primarily by targeting the mechanisms by which neurons send signals to one another.

However, as many as 30 percent of people with epilepsy do not respond to current drugs, making the search for additional drugs that act by different mechanisms an urgent one.

Enter Galanin

A promising new approach to treating seizures is to target a molecule called galanin. Galanin is a peptide, a fragment of a protein, produced in the brain to regulate a variety of functions, such as pain, memory, addition, mood, and appetite. In the late 1990s, researchers discovered that galanin is also a potent anticonvulsant.

Recent research suggests that when seizures occur the brain steps up production of galanin, possibly as a way to protect itself against the seizures. As a result, mice engineered to lack galanin are more susceptible to developing seizures.

Because galanin seems to play a role in reducing seizures, several groups of researchers, including those at Scripps Research, have been working to develop drugs that target the galanin system.

The first category of such compounds consists of synthetic molecules that mimic galanin's functions (called agonists) and include Galnon, developed by Bartfai's group. Galnon and other galanin agonists have been shown to act as anticonvulsants when given to animals that were rendered prone to developing seizures. But these agonists have several drawbacks as potential therapeutic agents. For one thing, because Galnon acts relatively broadly, it may have unwanted side effects.

A New Mechanism

Lu, Roberts, Bartfai, and colleagues at Scripps Research have now designed a compound that targets the galanin system but, unlike the previous agonists, is more selective in its action. The compound, dubbed CYM2503, binds to one of the three receptors for galanin on nerve cells, the galanin receptor type 2 (GalR2). On its own, CYM2503 has no effect on GalR2, but when galanin also binds to the receptor, CYM2503 boosts galanin's function.

The researchers tested the effects of CYM2503 on mice and rats that had received a chemical causing them to have seizures. The animals that received CYM2503 took longer to get the seizures and, when they did, the seizures lasted for a shorter time. Most importantly, when the researchers looked at the animals after 24 hours, the rats that had been treated with CYM2503 had a dramatically higher survival rate than those that had not.

This mechanism of action, modifying a receptor's function, is common to many successful drugs that have been developed for the treatment of a number of conditions, including epilepsy, hyperparathyroidism, and AIDS, but not yet for drug candidates targeting galanin system.

"It is a double breakthrough," says Bartfai. "The compound is a first new mode-of-action anticonvulsant and it represents a new mechanism of molecular action."

Because CYM2503 only works when galanin, a natural molecule, is also present, the researchers predict it will have fewer side effects than drugs that work on their own. This study provides the first evidence that modulating the GalR2 receptor is an effective strategy for treating seizures, thus opening the door for the development of drugs that target this mechanism.

"Based on the known functions of the GalR2 receptors, it may also work in treating depression and in protecting the brain from damage," says Lu.

Roberts adds, "This is an area we can now move into. We plan to go systematically through other conditions."


'/>"/>

Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

Related biology news :

1. Scripps research study shows infectious prions can arise spontaneously in normal brain tissue
2. Scripps Research scientists find new way to attack cancerous cells
3. Scripps research scientists determine structure of immune molecule that counteracts HIV strains
4. Scripps Research scientists break barrier to creating potential therapeutic molecules
5. Team led by Scripps Research scientists discovers bodys own molecular protection against arthritis
6. American Society for Microbiology to honor Scripps, Claude ZoBell
7. Scripps Research study overturns decade-old findings in neurobiology
8. Scripps research scientists shed light on potential treatment for Gauchers disease
9. Scripps Research team provides groundbreaking new understanding of stem cells
10. New Scripps Research and GNF study helps explain how we can sense temperatures
11. Scripps Research scientists reveal how genetic mutations may cause type 1 diabetes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... 28, 2016 First quarter 2016:   ... compared with the first quarter of 2015 The gross ... M (loss: 18.8) and the operating margin was 40% (-13) ... Cash flow from operations was SEK 249.9 M (21.2) , ... is unchanged, SEK 7,000-8,500 M. The operating margin for ...
(Date:4/19/2016)... , UAE, April 20, 2016 ... be implemented as a compact web-based "all-in-one" system solution ... the biometric fingerprint reader or the door interface with ... of modern access control systems. The minimal dimensions of ... ID readers into the building installations offer considerable freedom ...
(Date:4/14/2016)... 14, 2016 BioCatch ™, ... today announced the appointment of Eyal Goldwerger ... Goldwerger,s leadership appointment comes at a time ... the deployment of its platform at several of the ... which discerns unique cognitive and physiological factors, is a ...
Breaking Biology News(10 mins):
(Date:5/26/2016)... (PRWEB) , ... May 26, 2016 , ... ... developed by Medistem Panama Inc. at the City of Knowledge in ... tissue-derived mesenchymal stem cells in the US earlier this year following FDA approval ...
(Date:5/25/2016)... ... May 25, 2016 , ... ... delegation at BIO 2016 in San Francisco. Located at booth number 7301, representatives ... to answer questions and discuss the Thai biotechnology and life sciences sector. ...
(Date:5/25/2016)... ... ... Scientists at the University of Athens say they have evidence that the variety of ... could lead to one good one. Surviving Mesothelioma has just posted an article on ... evaluated 98 mesothelioma patients who got a second kind of drug therapy ...
(Date:5/24/2016)... , ... May 24, 2016 , ... ... diabetes, and traumatic injuries, will be accelerated by research at Worcester Polytechnic Institute ... engines of wound healing and tissue regeneration. , The novel method, developed by ...
Breaking Biology Technology: