Osteoporosis drugs found to combat malaria, other diseases

CHAMPAIGN, Ill. — A series of bisphosphonate drugs already approved to treat osteoporosis and other bone disorders in humans carry potent anti-parasitic activity, offering a new approach to the treatment of malaria, sleeping sickness and AIDS-related infections such as toxoplasmosis.

Researchers from the University of Illinois, the Venezuelan Institute for Scientific Research in Caracas and the London School of Hygiene and Tropical Medicine report their findings in the March 15 issue of the Journal of Medicinal Chemistry. The paper is online at the journal’s Web site.

“It’s a very welcome development to find a class of compounds that have strong anti-parasitic activity and are already approved for use in humans,” said Eric Oldfield, a UI professor of chemistry and biophysics. “New drugs are urgently required in the less developed nations, since the parasites are becoming drug resistant at an alarming rate. And many of the current drugs are either too expensive or too toxic to be used routinely.”

Oldfield and veterinary pathobiology professors Roberto Docampo and Silvia Moreno led a team of eight UI researchers on the paper. Julio A. Urbina and Simon L. Croft headed the teams from Venezuela and London, respectively.

Parasitic protozoan diseases are the world’s most widely spread human health problem. An estimated 3 billion people suffer from one or more parasitic infections. Plasmodium falciparum, the causative agent of malaria, infects 500 million people a year, resulting in 2 million to 3 million deaths a year, while Trypanosoma brucei, Trypanosoma cruzi and Leishmania species cause 20 million disease cases annually. The organism Toxoplasma gondii is the causative agent of AIDS-encephalitis.

The most common treatments for these parasitic diseases often cause adverse side effects, requiring a stoppage of treatment. The bisphosphonate drugs are active against the causative agents of African sleeping sickness, Chagas’ disease, malaria, leishmaniasis and toxoplasmosis, the scientists found. The drugs – such as Merck’s Fosamax, Procter & Gamble’s Actonel and Novartis’ Aredia – act much as they do in inhibiting bone resorption, by targeting and inhibiting a specific enzyme, farnesylpyrophsophate synthase, in the parasites. The names of the three drugs are registered trademarks of their respective manufacturers.

The specificity is thought to be due in part to enhanced uptake into specialized granules called acidocalcisomes, which were discovered by Docampo and Moreno and are present in all of the parasitic cells. “These granules are chemically similar to bone,” Docampo said, “and we think this may contribute to drug uptake and selectivity.”

The National Institutes of Health, World Health Organization, Burroughs Wellcome Fund, Howard Hughes Medical Institutes and the American Heart Association, Midwest, funded the work.