While open access to publications and data sets has become increasingly common, providing free access to a small library of physical compounds with associated data and advice had never been attempted until MMV’s Malaria Box was launched in 2011. By freely providing 400 diverse molecules active against malaria, the project showed there was a real appetite from researchers for compounds to evaluate. Based on this success, MMV launched the Pathogen Box with 400 different compounds active against malaria or one of a range of neglected disease pathogens.
To support research on these two boxes of compounds, particularly in disease-endemic countries, MMV awarded seven challenge grants to researchers working on each of them. In 2016, all of the Pathogen Box grant recipients, together with four additional runners-up, were invited to attend a 2-day drug discovery workshop organized by MMV, the Cape-Town based H3D Drug Discovery Centre and the South African Medical Research Council at the International Conference on Pure and Applied Chemistry 2016 in Mauritius. Through these initiatives we aim to not only provide access to compounds but also create an open and collaborative forum for researchers.
Dr Benoît Laleu explains the progress of research spurred by these initiatives as well as the key learnings.
1. To date 180 Pathogen Boxes have been dispatched; how is research with the molecules progressing?
Excitingly, we saw results just one month after the box was launched. Prof. Robin Gasser at the University of Melbourne screened the compounds against parasitic worms and identified one compound in particular that was highly active. Thanks to funding from the Wellcome Trust and through the Australian Research Council Linkage Project initiative, the compound is undergoing further research.
To date, 23 groups have shared their findings with us and two articles have been published.1,2 We have also been able to link different groups working on the same diseases as well as those with complementary results. This helps them to learn from each other’s findings.
By providing not only compounds, but medicinal chemistry advice and further information on the compounds, we have been able to support several research groups to apply for independent funding. This is particularly exciting for those diseases that have been severely neglected such as eumycetoma – a fungal infection with only a 35% cure rate using antifungals and surgery.
2. How are these initiatives helping to seed endemic-country research capacity?
Of the 180 Pathogen Boxes dispatched, 50 have gone to countries where malaria and/or other neglected diseases are endemic.
The challenge grants for the Malaria Box and Exploiting the Pathogen Box have really helped to build capacity. For example, Dr Fabrice Boyom in Cameroon received further funding from the British Society for Antimicrobial Chemotherapy to continue his research on toxoplasmosis, thanks to the quality of his findings researching the Malaria Box with the grant he received. This is also an example of how the next generation is getting trained and involved. Fabrice is now working with seven young researchers including PhD students.
3. What key learnings have MMV made through these projects that could be applied to similar initiatives in the future?
Based on the demand for the two boxes, it is clear that researchers are interested in receiving active compounds for their work. Other key learnings are that:
- It’s important to include non-commercially available compounds in the boxes, as they provide more novelty versus those commercially available (which have been previously researched).
- Researchers often require additional copies and so we need a reasonable stock of compounds.
- Most of the researchers that request the boxes are biologists and so require medicinal chemistry advice and input to be able to progress their research.
- As we learnt early on with the Malaria Box, compounds can be repurposed against different diseases.
With these learnings in mind, our next initiative is the Pandemic Box, which will include antiviral and antibiotic compounds, again at no cost to researchers. The goal here is to provide chemical starting points for drug discovery for diseases like Zika and Ebola as well as to repurpose compounds for malaria and neglected diseases. This will be a joint project between MMV and the Drugs for Neglected Diseases initiative.
- Preston S et al. “Screening of the 'Pathogen Box' identifies an approved pesticide with major anthelmintic activity against the barber's pole worm.” Int J Parasitol Drugs Drug Resist. 6(3):329-334 (2016).
- Vila T et al. “Screening the Pathogen Box for identification of Candida albicans biofilm inhibitors.” Antimicrob Agents Chemother. 61(1) (2016).