Many of the drugs we use to fight infections lose their effectiveness as the targeted pathogens acquire resistance to them. So researchers have begun adopting a new strategy. Instead of using drugs to kill the offending pathogens, they're trying to design drugs that can block their entry into human cells before they can cause disease.
Sooner or later, says Abhay Satoskar, a professor of pathology at Ohio State University, drug resistance becomes a problem in the battle against disease-causing organisms or pathogens. “Any time you have an agent that targets a pathogen, the pathogens are smart and eventually come up with a strategy to make that drug or agent ineffective,” said Satoskar.
Most bacteria, viruses and parasites must enter human immune system cells to reproduce and cause illness. Satoskar is leading an effort at Ohio State to develop a compound that blocks a pathogen’s entry into the cells.
The experimental drug targets a natural cell enzyme, called P13K, that allows pathogens to pass through the cell wall. The compound changes the chemical activity of P13K, blocking entry into cells.
The team demonstrated the effectiveness of the cell-blocking strategy with the parasite that causes leishmaniasis, a tropical illness caused by a parasite transmitted in the bite of a sand fly. Also known as leishmania, an estimated 1.5 million new cases are diagnosed each year. The disease causes disfiguring open sores on the skin. Not only is the illness indigenous in many parts of the world, but experts say it is now turning up in U.S. troops returning home from Afghanistan.
There is a drug to treat leishmania, says Satoskar, that’s up to 90 percent effective in curing the disease. But Satoskar says the medication has a lot of side effects, including anemia, weight loss and neurological problems, and many people don’t complete the 21-day course of injections.
Using laboratory mice, Satoskar says researchers compared the effectiveness of the existing drug to the targeted, therapy his team is developing. Satoskar says the new agent worked just as well in treating leishmania, and the cell-blocking strategy could potentially work against other disease-causing organisms or pathogens.
“Now the issue is how to do you fine-tune it? And that could be fine tune(d) based on different pathogens, because different pathogens could use different pathways to get in,” Satoskar said.
Satoskar also is interested in learning whether the experimental compound could be used as a skin spray to prevent infection with leishmania when someone is bitten by a sand fly.
An article on preventing leishmania by blocking parasites from mice immune cells is published in the journal Proceedings of the National Academy of Sciences.