"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, PhD, professor of pharmacology and drug discovery at UC 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, which initially included the Harvard TH Chan School of Public Health, Columbia University, GlaxoSmith Kline and Washington University, is to systematically look for drug-able proteins encoded by the parasite's genome, primarily using in vitro evolution and whole genome sequencing."
Malaria is a global scourge. Roughly half of the world's population live in areas at risk of malaria transmission. In 2015, according to the World Health Organization, more than 214 million clinical cases of malarial infection were reported, with 438,000 deaths. The vast majority of deaths occur in Africa, killing children.
Winzeler and colleagues have focused their efforts upon 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' life-cycle 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.
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 Pennsylvania State University 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.
Provided by University of California - San Diego
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