The body's own marijuana as inspiration for drug research
Endocannabinoids - the body's own marijuana - are promising departure points for drug research. Professor of Molecular Physiology Mario van der Stelt examines whether inhibiting their production can be a way to fight inflammatory brain disease and to combat obesity. Inaugural lecture 19 October.
Endocannabinoids are produced in the brain and they control communication between nerve cells. They play a role in pain, eating habits, stress, memory and anxiety disorders. These substances may also serve as the starting point for the development of new medicines. Van der Stelt believes universities have an important task in pre-clinical research because the costs of developing a new medicine are enormously high; they can cost over two billion euros.
Efficient measurement methods
This development process can be made more efficient through the use of innovative screening methods using advanced algorithms. Leiden chemists have devised a measurement method in which they can chart the working of a substance in a living cell or tissue - known as Activity-Based Protein Profiling (ABPP). Leiden chemists have applied this method in their research on an experimental drug developed by a Portuguese pharmaceutical company that cost a healthy volunteer his life in a phase 1 study. Van der Stelt's research group also uses this method in research on the working of the body's own marijuana.
Using the ABPP measurement method, Van der Stelt has found an efficient way of identifying new substances that can inhibit the production of the 2-AG endocannabinoid. In partnership with researchers Patrick Rensen andSander Kooijman from the LUMC, it has been demonstrated that these inhibitory substances can suppress appetite. The Leiden researchers also found indications that they can inhibit inflammations in the brain using the chemical compounds they have developed. The team has now applied for two patents.
Conversely, an increase in 2-AG concentration can help combat anxiety disorders. Van der Stelt's research group is therefore working on developing substances that combat the breakdown of 2-AG. Such inhibitors are very promising: American Bio-tech company Abide has already developed an experimental drug containing an inhibitor that reduces the tics in patients suffering from Gilles-de La Tourette syndrome.
Van der Stelt's group is also conducting research on herbal marijuana. Certain components of marijuana have been prescribed for many years as an experimental medicine to MS patients, among others, to reduce their spasms and to AIDS and cancer patients to stimulate their appetite. 'The scientific evidence is very tenuous and the pharmaceutical companies are hardly doing any more research because they cannot apply for a patent on marijuana,' Van der Stelt explains.
Cheaper and safer alternative
His research group has mapped the 'gold standard' for improving pre-clinical research on cannabinoid receptors. This will make it possible to determine at an earlier stage whether possible substances for medicines have the desired effect and the best candidate medicines for expensive clinical trials can be selected also at an earlier stage, Van der Stelt explains.