The new resin acid molecule has promising properties as a potential drug for epilepsy

Developed by researchers at Linköping University, the new molecule has promising properties as a potential drug for epilepsy.Studies published in the journal Epilepsy It has been shown that some molecules have anti-seizure effects.

In patients with epilepsy, nerve cells in the brain become overactive, causing epileptic seizures.

More than 60 million people worldwide suffer from epilepsy. One-third of them have seizures after taking the drug, and there is an urgent need for a new type of drug. “

Nina Ottosson, Senior Research Engineer, Faculty of Biomedical Sciences, Linköping University

Nerve impulses are electrical signals that travel along nerves at the speed of lightning. Epilepsy and some other conditions occur when nerves transmit too much signal and must be electrically quiet. Nerve impulses are created when small channels, called ion channels, in the membrane of nerve cells pass through charged ions. When a sufficient number of ions enter a cell, an electrical impulse is generated, transmitted along long nerve fibers and subsequently stimulates other nerve cells. Thus, ion channels play an important role in epilepsy. Many of the drugs currently used to prevent epileptic seizures work by affecting ion channels.

Previous studies by a research group at Linköping University have shown that the resin acids found in the resin of pine and spruce trees can affect certain types of ion channels. Scientists have started with these natural resin acids to develop new similar molecules. The long-term goal is to develop drugs that prevent epileptic seizures.

In a newly published study, researchers looked at ion channels that affect the ease of stimulation of nerve impulses. This channel, the potassium ion channel shown in hKV7.2 / 7.3, plays an important role in epilepsy. Epileptic seizures can occur when closed, but can be stopped when the channel is open. One drug, retigabin, was able to open hKV7.2 / 7.3, which helped treat severe epilepsy. However, retigabin affects other ion channels, especially smooth muscle channels found in the bladder and blood vessels. This has had undesired effects such as abnormal hypotension and difficulty urinating. Retigabin was discontinued a few years ago.

Researchers have shown that some of the new resin acid molecules can open hKV7.2 / 7.3. They also investigated whether the molecule affects the closely related ion channel, hKV7.4. hKV7.4 is opened by retigabin and contributes to its undesired effect. Experiments with rat tissue have shown that new molecules have less effect on smooth muscle and are less likely to have undesired effects on blood vessels and bladder. The new resin acid affects ion channels using a mechanism different from that used by retigabin. Researchers believe that different mechanisms of action are important for their effectiveness in different tissues.

“We believe that the mechanism by which our molecule acts on ion channels is very important. Through future collaboration, we will guide our molecule to clinical use of medicines along a complete pathway. I hope we can do that, “says Nina Ottosson.

Another important question is whether the new molecule can prevent seizures throughout the body. Researchers then investigated the effects of molecules on zebrafish larvae that used special substances to cause seizures.

“In these experiments, some molecules showed antiepileptic effects when used at the same concentration as retigabin,” said Nina Ottosson.

Scientists are currently working on a detailed understanding of how resinic acid molecules affect ion channels and how to improve them for medicinal use.

“Patients and relatives often contact us, but their story shows how urgent the need for effective treatment is. Some of the people affected by our study It would be great if helped in the long run, but at the same time we must be aware of how difficult it is to guide the molecule along the complete path to a new drug. Our results are , May contribute to development by stimulating other research.

This study was conducted in collaboration with researchers at Sophion Biosciences A / S in Denmark and the University of Copenhagen. The zebrafish experiment was conducted in collaboration with Bioreperia AB. Research funding comes from the Swedish Research Council, the Swedish Cardiopulmonary Foundation, the Swedish Brain Foundation, Novo Nodisc Fonden, Parkinson’s Stiftersen and others. Some researchers have applied for a patent for the resin acid molecule described in the study.