Gates Foundation grant boosts malaria research program

A false-color electron micrograph of a malaria-causing Plasmodium parasite infecting a mosquito. Credit: Margaret Shear / WikipediaAll Rights Reserved.

UNIVERSITY PARK, Pa. — An international team, including researchers at Penn State, have received a three-year, $4.7 million supplemental grant from the Bill & Melinda Gates Foundation to advance their development of improved therapies for malaria eradication.

“This new funding will allow my lab to continue to pursue and expand the work we have been doing to help advance the most promising future antimalarial drugs toward development and clinical trials,” said Manuel Llinás, professor of biochemistry and molecular biology and leader of the research team at Penn State.

Malaria is a global scourge and roughly half of the world’s population live in areas at risk of malaria transmission. According to the World Health Organization, more than 214 million clinical cases of malarial infection were reported in 2015, with 438,000 deaths. The vast majority of these deaths are children and occur in Africa.

“The very long term goals are to accelerate the development of novel treatments and preventative medicines that can be used to assist with malaria eradication and elimination, and which can serve as replacements for current drugs that are losing efficacy,” said Elizabeth Winzeler, professor of pharmacology and drug discovery at the University of California, San Diego School of Medicine and the grant’s lead scientist. “The grant will support a multinational consortium, with leadership at UC San Diego, which aims to speed antimalarial drug development. The objective of the consortium is to systematically look for drug-able proteins encoded by the parasite’s genome, primarily using in vitro evolution and whole genome sequencing.”

The Llinás lab at Penn State is contributing to these efforts by determining how the newly-developed drugs work. They have developed methods using mass spectrometry to measure the malaria parasite’s response when exposed to a drug.  The results of their research will help to predict the target proteins affected by these next-generation antimalarial drugs.

The research team has focused their efforts on drugs that target the disease-causing Plasmodium parasites that infect Anopheles mosquitoes, which then transmit the parasite to humans through their bite. While prevention and treatment of malaria has significantly advanced, the parasites themselves remain an elusive target.

The parasites’ lifecycle complicates the problem. Most current drugs are effective at only certain stages of parasite development, allowing infections to recur. The only licensed antimalarial drug capable of fully cleansing an infection and eliminating the possibility of relapse can have serious, life-threatening side effects. And the parasites tend to quickly evolve resistance to drugs used against them.

“One way to potentially circumvent resistance is to understand in detail how these drugs work to kill the parasite,” said Llinás. “This allows for better targeting of the drugs and proper formulation of drug combinations to be used for antimalarial treatment.”

In 2012, the Gates Foundation awarded Winzeler and colleagues a four-year, $3.5 million grant to develop new antimalarial compounds less likely to provoke resistance compared to existing drugs. The supplemental grant is intended to advance and broaden the scope of work, and includes new research partners, such as Penn State and the Wellcome Trust Sanger Institute in the United Kingdom.

Winzeler said the past three years have been productive. Researchers have produced the most comprehensive study of malaria parasite drug resistance to date, created more than 200 drug-resistant laboratory clones of the P. falciparum parasite against which to test potentially therapeutic small molecule compounds and identified 12 new targets for anti-malarial drug discovery and development; developed a robust bioinformatics pipeline through which researchers can share data and findings; discovered new alleles -- alternative forms -- in known drug-resistant parasite genes; and discovered new drug-resistant genes.

In addition to Penn State, UC San Diego, and the Wellcome Trust Sanger Institute, the international collaboration includes researchers at the Harvard T.H. Chan School of Public Health, Columbia University, GlaxoSmithKline, and Washington University.

Last Updated March 06, 2017