A novel approach to detecting interactions between scorpion venom and its target molecule could aid in the discovery of new drugs for treatment of a wide range of nerve disorders.
A major therapeutic target for drugs in the body is a type of molecule called a sodium channel. These tiny pores control the flow of charged particles in and out of the cell, which for example is how electrical signals are generated and passed along our nerves.
When these channels malfunction they can cause serious problems, ranging from heart defects to epilepsy. They’re a promising target for treatment of these diseases, but they’re difficult to study because the protein is very large and complex. A team from Johns Hopkins and Aix Marseille Universities has devised a novel way to look for new drugs to correct sodium channel function.
“Our idea was, can we take out just a little piece of that big molecule and study that in isolation,” explains Dr. Frank Bosmans. “We needed a molecule that also interacts with that small region. For that we chose these scorpion toxins because they have evolved for millions of years to very specifically target a certain region within this sodium channel.”
Scorpion toxins target a specific, very important section of the sodium channel molecule, and by focusing on just that section the team could search for other molecules that target the same area. They were able to reproduce many copies of the fragment and attach them to a sensor chip which could then be used to screen potential drug molecules to see if any are capable of interacting with that part of the sodium channel, altering its activity, and so might be useful in treating associated medical conditions.
More importantly, this method will help make more selective drugs with fewer side effects, because the fragment in question occurs in several different versions, which vary in their abundance in different parts of the body. This means that it’s possible to create a drug that, for example, will treat epilepsy by targeting the sodium channels in the brain, but leaves the ones in the heart untouched.
“The more specific you can design a drug the less side effects you’ll get,” continues Dr. Bosmans. “It’s always going to be challenging but at least the better your initial steps are the higher chances are that you’ll actually find something that has little or no side effects.”