17 June 2014

Africa: Project That Mails Antimalarial Boxes to Start Spin-Off

Photo: Gates Foundation
Blood samples being prepared for analysis as part of a malaria trial (file photo).

An initiative that mails a box of antimalarial compounds for free to scientists around the world has helped boost research on drug discovery and development since its launch in 2011 and inspired a second project for neglected tropical diseases, according to product-development partnership the Medicines for Malaria Venture (MMV).

The Malaria Box contains samples of 400 compounds that are active against malaria, with enough of each compound to run up to ten experiments. The boxes have so far been shipped to dozens of scientists, including those in Africa, Asia and South America, and have resulted in nine peer reviewed papers and unexpected discoveries on diseases other than malaria.

Now MMV and its partners wish to capitalise on this success by launching a Pathogen Box by the end of 2015 to tackle an even broader range of neglected tropical diseases, such as tuberculosis and schistosomiasis.

"It's about getting the right compounds into the right labs - providing researchers with a head start by selecting and making available the most promising compounds," says Paul Willis, project director in drug discovery at MMV.

From data to compounds

The project's origins lie with MMV initially publishing open-access data on around 20,000 compounds that showed antimalarial activity, having analysed about four million compounds from a range of chemical libraries.

But Willis says the impact of simply opening up data "wasn't as high as had been hoped" as researchers wanted to run their own experiments and needed the actual physical compounds - not just their chemical structures - given that they are difficult and expensive to make.

"The idea [for the box] was to distil these 20,000 compounds down into a more manageable 400 that were more accessible and amenable for researchers to start working with," he says.

The list was carefully selected, first by computer analysis and then by chemists, to include molecules with a broad spectrum of chemical structures, physical properties and biological activity from the original long list.

Half are drug-like compounds for oral drug discovery and half are for use as tools to study the parasites.

The only condition for receiving a free box is that researchers must release any results into the public domain within two years.

Promising results

"We started to see results really very quickly, where people were sending us back information," says Willis.

There have been nine resulting publications in peer-reviewed journals plus other unpublished results deposited into an open-access database, ChEMBL, funded mainly by the Wellcome Trust.

To date, 177 Malaria Boxes have been supplied, including ten to Africa, 15 to Asia and three to South America.

About 70 per cent of the researchers focused on malaria, but the remainder used the box to study neglected tropical diseases and infectious diseases, as the compounds showed unexpected activity against other pathogens.

For example, Christopher Huston, an infectious disease researcher at the University of Vermont, United States, used the box to publish results he hopes may lead to a treatment for cryptosporidiosis - the second most common cause of life-threatening diarrhoea in children under the age of one.

Robert Don, discovery and preclinical director at the Drugs for Neglected Diseases initiative, says his organisation has screened Malaria Box compounds against parasites that cause sleeping sickness, Chagas' disease and visceral leishmaniasis.

"Open access to compounds, data and intellectual property saves time and facilitates collaborative research activities through rapid sharing of data among project partners, in addition to reducing duplication of research efforts," he tells SciDev.Net.

Huston adds that it is relatively difficult to access high-quality compounds to screen for potential drug leads, and the cost of constructing a library of drugs such as the Malaria Box is prohibitive for a single small lab.

Fabrice Boyom, head of the Antimicrobial Agents Unit at the University of Yaoundé, Cameroon, says the boxes negate the need for "highly sophisticated and costly equipment that is not always available in the developing world".

Colin Sutherland, head of the Immunology and Infection Department at the London School of Hygiene & Tropical Medicine in the United Kingdom, says: "Offering a free box is an important step in opening up the screening end of the drug development pipeline to more players."

But he cautions that the success of the Malaria Box project "will be judged on whether we get any new drugs out of it".

"It is important to see how many of the 400 compounds progress from the first stages of screening," he adds.

Outside the box

Willis of MMV tells SciDev.Net that the new Pathogen Box will also contain around 400 compounds.

"This free box will take us to the next level as the potential and power [to tackle neglected tropical diseases] could be even greater," he says.

MMV is using various methods to select the box's contents, including consulting researchers from the neglected tropical disease community. An expert committee will make the final selection.

Sutherland tells SciDev.Net that the next focus should be identifying a further set of 400 compounds for screening against neglected tropical diseases - to keep the pipeline "stoked" with new compounds coming through.

Link to Malaria Box

Link to Pathogen Box

See video by MMV about Malaria Box.

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