Osteoporosis drugs strengthen bones, but it looks like they can also be modified to strengthen the body’s defenses against malaria.
The parasite that causes malaria has a knack for evolving resistance to the drugs used to combat it, so scientists are always on the hunt for new weapons against this deadly disease. Now, Illinois researchers have found possibilities among an unlikely source—Actonel (Risedronate) and Zometa (Zoledronate), the drugs used for osteoporosis.
These drugs are commonly used to fight the degenerative disease that reduces bone density, and normally they cannot cross the membrane of red blood cells to get at malaria parasites. But Illinois researchers chemically altered the drugs and found that they can kill the malaria parasite.
The modified form has a long “lipid tail” that enables them to pass through the lipid-rich membrane of red blood cells and bind to the parasite’s target enzyme, says Eric Oldfield, the LAS chemistry professor who led the study. What’s more, the modified drugs work at low concentrations and have no observed toxicity to the mice in the study.
The World Health Organization estimates that malaria killed 708,000 to 1.003 million people in 2008, most of them in Sub-Saharan Africa and Asia. However, the malaria parasite has evolved resistance to nearly every drug used so far to combat it. Some of these drugs still work, especially when used in combination, Oldfield says, but drug-resistant malaria strains are always emerging.
“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,” he says. “The parasites mutate and then you lose your malaria drug.”
The modified osteoporosis drugs work by targeting the geranylgeranyl diphosphate synthase (GGPPS) enzyme, which the parasite relies on to protect itself from a person’s immune system.
“We are the first to show that the enzyme GGPPS is a valid target for malaria,” says Yonghui Zhang, a research scientist in Oldfield’s lab and inventor of the lead compound, BPH-703. “Our work gives new direction to finding new anti-malarial drugs.”
