US researchers including one of Indian origin have found malaria-fighting properties in cancer drugs.
Caused by parasites belonging to Plasmodium species and transmitted by the bite of infected mosquitoes, malaria is life-threatening and is one of the world’s most common infectious diseases.
It is responsible for over 600,000 deaths per year, predominantly in sub-Saharan Africa. About 80 per cent of these deaths are children under age 5.
“Over time, genetic mutation of the malaria parasite makes it resistant to current drugs,” said molecular parasitologist Debopam Chakrabarti at University of Central Florida.
“The World Health Organization reported that malaria parasites are increasingly becoming resistant to the current therapy used to treat malaria, which was discovered in the 1990s. So, new and more effective drugs for malaria are long overdue as about 30 years have gone by since we have had a new class of compounds in the market against malaria,” he added.
But drug discoveries can take years, even decades, Chakrabarti explained, as compounds go through many phases of testing for efficacy and safety.
“One of the ways we can accelerate the discovery of new treatment options is to use existing drugs that are already approved by the Food and Drug Administration,” Chakrabarti said.
“This is called taking a piggyback approach, looking at existing drugs that are already on the market to see if they have antimalarial properties. This will help to shorten the initial stages of drug discovery which is usually quite time-consuming.”
To meet the urgent need for new drugs, the team decided to repurpose protein kinase inhibitors — drugs originally developed for cancer treatment — for an accelerated path to drug therapy for malaria.
Protein kinases are enzymes that regulate proteins in the body and are heavily targeted for cancer and other disease therapies by the pharmaceutical industry. Protein kinases are very important for the malaria parasite’s life cycle and as such make good drug targets.
The team tested a range of anti-cancer protein kinase inhibitors to identify inhibitors that are known to target human Polo-like kinase, a type of protein kinase that plays an important role in cell division in humans.
They discovered that a group of inhibitors, specifically BI-2536, a known human Polo-like kinase 1 inhibitor, exhibited strong antimalarial properties.
“While the malaria parasite plasmodium does not have Polo-like kinases, the protein kinase inhibitors target another family of proteins called NEK, which also regulate cell division,” said doctoral candidate Monica Bohmer, part of Chakrabarti’s team.
“They also targeted other stress-response pathways which helped to kill the parasite.” She added that future studies will explore the functions of these NEK proteins in the parasite.
“Overall, this study provides valuable insights for the potential of repurposing of protein kinase inhibitors for malaria treatment,” Chakrabarti said, “while also underscores the need for further research to identify additional targets and optimise the efficacy of these inhibitors.”
The findings are published in the ACS Infectious Diseases journal.
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