Collaborative Networks

(August 18th, 2016) A creative project, providing open access to 400 compounds with potential effects against malaria, recently resulted in more than a dozen drug development projects. Could this open source approach herald a new era for drug discovery?

Not least since the last Nobel Prize, malaria is back on the research agenda. Although treatment options exist - the WHO recommends artemisinin-based combination therapies - in certain areas, such as Cambodia and Thailand, the pathogenic parasite, Plasmodium falciparum, has developed resistance to the drugs. New medicines are desperately needed and this is where the Medicines for Malaria Venture (MMV) project steps in. Their mission: “reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of new, effective and affordable antimalarial drugs”.

To fulfill their mission, the project members got very creative. They assembled a Malaria Box, containing 400 commercially available compounds (selected from 25,000) with “confirmed activity against the blood-stage of P. falciparum” and made it available to research groups worldwide free of charge. The results from close to 300 assays from more than 50 groups were finally published and placed in the public domain to “help continue the virtuous cycle of research”.

Amongst others, participating research teams assessed the compounds’ safety on 73 human cell lines as well as developing zebra fish embryos. Teams also tested the substances with two recently developed in vitro models to profile for interaction with drug-metabolising enzymes and for acute hepatotoxicity. And biochemical screens for enzyme inhibition or protein-protein interactions revealed the substances’ mechanism of action. Data from 119 different assays identified potential targets for 135 of the 400 compounds.

Besides the effect on malaria, scientists screened the Malaria Box compounds also against 16 additional disease-causing protozoa as well as against helminths, mycobacteria, bacteria and even 59 human tumour cell lines.

Called the “first-ever test of open-source drug-discovery”, this test indeed turned out quite successful. Not less than 34% of the compounds were found to be effective, resulting in nine promising candidates for proof-of-concept studies in mice. All in all, the experiments ignited more than 30 drug development programmes for a variety of diseases. “The collective results are greater than the sum of the individual assays, because each compound can be queried for activity, pharmacokinetic and safety data,” the project members say. The drastic selection of nine compounds from 400, present the unquestionable advantages of shared forces in drug development. “The Malaria Box Project demonstrates how an open source approach allows effective data sharing: this publication serves as much to share the data among the 180+ co-authors as with the wider scientific community. By publishing in concert this ensures early publication and also sharing of ideas and expertise in drug discovery,” the scientists point out.

Following on from this open access approach, MMV is now distributing the Pathogen Box, containing 400 diverse, drug-like molecules active against neglected diseases of interest, such as Chagas, tuberculosis or river blindness. This, as the researchers hope, “can be the start of equally fruitful collaborative networks”.

Karin Lauschke


Last Changes: 09.12.2016