New application shows high success rate for malaria drug prediction
NOV. 15, 2017 (Seattle, Wash.) – Investigators at the Center for Infectious Disease (CID) Research and the Fred Hutchinson Cancer Research Center announced a new approach for identifying drugs that are effective against malaria. Researchers adapted an approach originally developed to perform cancer drug discovery to understand and drug malaria parasites. This discovery marks the first time the approach was applied to infectious disease research.
In a new study published in Nature Communications, researchers in the Kaushansky Lab at CID Research collaborated with the Gujral Lab at the Fred Hutchinson Cancer Research Center to combine experimental biology with computation to predict 47 proteins in the liver that are important for malaria parasite infection. The researchers also successfully predicted drugs that have been developed for other diseases that could be useful in preventing malaria infection.
Testing these predictions showed a very high success rate: over 80% of predicted proteins tested were validated. The success suggests that the approach can be expanded to identify drugs against other infectious diseases, making the process of drug discovery more efficient.
Maximizing data from small experiments is a critical issue in infectious disease research. On average, individuals afflicted with malaria live on $2/day, and the resources available to fight the disease are limited. Since malaria kills someone every minute, effective drug discovery efforts are also critical. This study demonstrates that the integration of computational tools with laboratory experiments can make the most of the limited resources available.
In a three-step process, researchers start by treating cells with a set of drugs that have known, overlapping activities against 300 human kinases. When drugs have different activities against the parasite computational tools can reveal which human kinases are important for infection. The logic process then is applied to hundreds of inhibitors, making predictions that are highly likely to be experimentally validated to reduce disease.
“This process is valuable because it can help scientists be much more resourceful with limited biological material and resources. We can now apply this approach to identify drugs that will be effective against isolates of malaria in the field and other diseases that are challenging to study in the lab,” said Dr. Elizabeth Glennon, postdoctoral scientist in the Kaushansky Lab.
With just one experiment designed to maximize possible results from small samples, this process identified nearly 50 candidates for potent malaria drugs. The researchers also identified drug compounds that have not been applied to malaria but are FDA-approved or in clinical trials for other uses. The paper also marks the first paper published from the Kaushansky Lab.
“This is an important starting point. It is our hope that this work will lead to a better understanding of how the malaria parasite is able to survive in humans and increase our ability to rapidly repurpose existing drugs to prevent and treat malaria. We hope this method can accelerate the rate of discovery for life-saving therapies for malaria and other diseases that take lives and cause suffering,” said Dr. Alexis Kaushansky, principal investigator.
ABOUT THE CENTER FOR INFECTIOUS DISEASE RESEARCH
The Center for Infectious Disease Research is the largest independent, non-profit organization in the U.S. focused solely on infectious disease research. Our research is the foundation for new drugs, vaccines and diagnostics that benefit those who need our help most: the fourteen million who will otherwise die each year from infectious diseases, including malaria, HIV/AIDS and tuberculosis. Founded in 1976, CID Research partners with key collaborators around the globe and strives to make discoveries that will save lives. For more information, visit www.cidresearch.org.
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