Osteoporosis drugs found to kill malaria parasites in mice

A research team at the University of Illinois led by chemistry professor Eric Oldfield has discovered that a chemically-modified form of two commonly prescribed osteoporosis drugs killed malaria parasites in mice.

The modified compound, called BPH-703, is able to impact the parasite's isoprenoid biosynthesis, which disrupts the sustenance and self-defense of the invading organism. By inhibiting the geranylgeranyl diphosphate synthase enzyme, the compound is able to make the parasite more susceptible to the patient's immune system.

"The lead compounds are chemically modified forms of the bisphosphonate osteoporosis drugs Actonel (Risedronate) and Zometa (Zoledronate)," Oldfield said. "The modified forms include a long lipid tail that helps them pass through the lipid-rich membrane of red blood cells, and also enhances the drug's ability to bind to the target enzyme, GGPPS."

The team viewed the properties of close to 1,000 substances to determine which substance could effectively stop the malaria parasite. Yonghui Zhang, a co-author of the study, invented BPH-703. Zhang said that the team was the first to identify the GGPPS enzyme as a possible target in the fight against malaria.

"It's important to find new drug targets because malaria drugs last only a few years, maybe 10 years, before you start to get resistance," Oldfield said. "The parasites mutate and then you lose your malaria drug."

Malaria is responsible for millions of deaths in more than 90 countries each year. While the World Health Organization and the Gates Foundation continue to increase the effort to eradicate malaria, drug-resistant strains of the disease continue to emerge. The potential of a non-toxic therapeutic is promising in the war against malaria.