The Malaria Box and Pathogen Box

The Malaria Box was launched in December 2011, in response to the need for scientists to have access to physical samples of molecules to initiate drug discovery programmes for malaria and neglected diseases. The Malaria Box contains 400 diverse molecules active against blood stage P. falciparum malaria, available free of charge on request. To date, more than 160 boxes have been despatched to 27 countries catalysing numerous drug discovery programmes.
Based on the success of the Malaria Box, MMV was awarded a grant from the Bill & Melinda Gates Foundation in 2013 for a follow-on project, the Pathogen Box. This new box will also contain up to 400 molecules for distribution to scientists, but this time they will be active not just against malaria, but also against one of a range of neglected diseases.
1. More than 160 Malaria Boxes have been distributed, how are they being used today?
Two thirds of the Malaria Boxes distributed are being used for malaria research and the other third on neglected diseases, such as sleeping sickness and Chagas disease. For malaria, the focus is on understanding the mechanisms of action of the molecules. While those working on other diseases are looking to test the molecules for activity against their organisms of choice.
2. How successful has the Malaria Box been so far?
There have been many exciting findings already and this is just the beginning. For example, researchers from the University of Vermont tested the Malaria Box compounds against Cryptosporidium, a parasite that causes diarrhoea and is from the same family as Plasmodium. They identified three active molecules, which led to a publication1 and funding to begin a medicinal chemistry programme. There are similar stories for schistosomiasis2 with the Swiss Tropical and Public Health Institute (TPH) and the London School of Hygiene & Tropical Medicine; and collaboration between the University of Antwerp, Swiss TPH and DNDi on human African trypanosomiasis.
3. Why do you believe it has been successful?
It is the first initiative of its kind, where a set of bioactive chemicals are given away for free to catalyse neglected disease drug discovery. More than that, the Malaria Box bridges the worlds of biology and chemistry to initiate new drug discovery programmes. The box breaks down the financial and technical barriers of accessing the most promising molecules.
4. What were the most valuable lessons you learnt from the Malaria Box project that you will apply to the Pathogen Box?
The main thing we learnt is that there is a huge need for molecules to be made available for neglected disease research. Researchers are eager to test molecules and eager to receive advice. Once biologists have screened the compounds, they need to be able to come back and seek medicinal chemistry advice. The other crucial component is for researchers to share their findings and data within the community in a reasonable time frame to encourage the research community to collaborate to help drive the research forward. To respond to this need, we worked together with ChEMBL, creating a one-stop shop for all malaria data.
5. What are the next steps for the Malaria Box and the Pathogen Box?
For the Malaria Box we are focused on gathering, mining and encouraging recipients to share their data and initiate new programmes. For the Pathogen Box we are in the process of determining which molecules to select. This is where we need input from the whole neglected diseases community, as MMV’s experience is of course focused on malaria. We aim to launch the Pathogen Box in 2015.
1. Bessoff K et al. “Identification of Cryptosporidium parvum active chemical series by repurposing the Open Access Malaria Box.” Antimicrob Agents Chemother. Feb 24 (2014).
2. Ingram-Sieber K et al. “Orally Active Antischistosomal Early Leads Identified from the Open Access Malaria Box.” PLoS Negl Trop Dis. 8(1): e2610 (2014).
Dr Thomas Spangenberg, Research Scientist, MMV