“The hit rates we have been getting are quite high. We still have to drill down to the good ones, but in terms of antibacterial activity we are seeing that about 10% of our extracts are active against gram positive and gram negatives,” said Marcel Jaspars of the University of Aberdeen, who leads the project, which began last year and is backed by more than €9.5m from the EU.
The scientists are zoning in on molecules which show promise in infection and inflammation and also in neurodegenerative conditions and difficult to treat diseases. Investigators at KU Leuven, Belgium, have uncovered some extracts that are extraordinarily active in assays they have for epilepsy and for central nervous system diseases. Meanwhile, partners in Tromso University in Norway are testing extracts against assays for cancer and inflammation, while Spanish partners are testing for antibacterial candidates.
“We are getting to the stage where we are seeing really good results and we are trying to de-convolute the chemistry,” Jaspers told in-Pharmatechnologist.com. “We have taken one or two molecules through to animal trials.”
Samples have been collected from the Irish sector of the Atlantic and also the Arctic, with plans in place to collect from the mid-Atlantic ridge this summer. The project will focus on returning samples from deep trenches, considered an interesting source of novel compounds because marine organisms here survive under extreme conditions. This autumn they will collect specimens from the Chile-Peru trench, around 8,000 metres down.
The team will take advantage of strategies commonly used in the salvage industry to carry out sampling, dropping samplers on a reel of cables to the trench bed. The scientists grow the unique bacteria and fungi from the sediment to isolate drug-like molecules for testing. Bacteria living within marine animals like sponges will also be analysed for interesting genes.
“Typically the kind of bacteria we are looking for are actinobacteria, because they are very high in biosynthetic pathways, but it turns out that even common-or-garden bacilli are producing some interesting chemistry,” said Jaspars. One bacillus has turned out a very interesting antibiotic, with a new kind of chemical structure.
Jaspars hopes the project will help drug discovery return to nature. “The key is to make the pipeline as efficient as possible to make it attractive for industry to want to investigate compounds from natural sources again. Because they have fallen out of love with it, despite the fact it gave them great drugs in the past,” he told us.
A meeting is scheduled this year for the 8
Jaspars is convinced that the project will yield new drug-like molecules for participating companies which could be developed with large pharma or licensed.