New measuring method facilitates drug research
Leiden chemical biologists led by Dr Mario van der Stelt have developed a method to facilitate the search for new drugs. This method has allowed them to take an important first step in the development of a drug against obesity.
The method, based on mass spectrometry, makes it possible to identify and quantify active proteins in complex tissues such as the brain. By measuring the activity of these proteins before and after administering a candidate drug, you can see at once how different proteins respond to the drug. This makes it possible to map a large number of biological targets of a candidate drug.
This method represents a new approach to drug research. Traditionally the pharmaceutical industry has only focused on a few possible off-targets that were suspected of being responsible for the potential side-effects of a drug. The new measuring method is called Comparative Chemoproteomics, and it was set up by PhD student Marc Baggelaar.
Using this method the researchers have discovered a new, highly selective substance in the brain that inhibits the production of the body’s own marihuana. The brain produces substances called endocannabinoids that have the same effect as THC, the psychoactive substance in marihuana. If the brain produces too many of these endocannabinoids, this can lead to overconsumption, overweight and inflammation in the brain. The selective inhibition of the production of endocannabinoids paves the way for a new drug for treating obesity, related metabolic diseases and inflammation of the brain.
‘We already knew from previous research that endocannabinoids play an important role in obesity,’ explains head researcher Mario van der Stelt. ‘Thanks to this new measuring method we have been able to determine in even more detail which specific molecules can inhibit the production of endocannabinoids.’ These molecules will form the starting point for developing a drug against obesity. The discovery has been patented in order to allow for further drug development.
This research was conducted in collaboration with brain researchers from the University of Amsterdam, the Italian research institute CNR and the American Scripps Research Institute (San Diego) and it has appeared in the leading Journal of American Chemical Society.
This research is partially funded by an ECHO grant of NWO Chemical Sciences and conducted in the framework of the ‘Endocannabinoids’ Faculty Profile Programme. This programme represents a collaboration between researchers from the Leiden Institute of Chemistry, the Leiden Academic Centre for Drug Research, and the Institute of Biology Leiden.
(29 May 2015)