Cattle drug may help tackle river blindness

9 March 2010

A veterinary drug that kills worms in cattle may also fight river blindness, a debilitating parasitic infection that afflicts 37 million people worldwide, researchers say. But experts caution against trying the compound in humans just yet. People contract river blindness, also known as onchocerciasis, when bitten by black flies that carry a nematode known as Onchocerca volvulus. The worm larvae mature and mate, producing up to 1000 "microfillariae" offspring per day, which migrate to the surface of the skin and to the eyes. When the microfillariae die, they cause itchy lesions that can lead to blindness. The disease often forces farmers to abandon lush river valleys rife with infected black flies for less fertile areas. Doctors currently treat river blindness with ivermectin, a drug that kills the microfillariae and lowers the fertility of the adult worms. Ivermectin has slashed cases of blindness and lesions in countries like Senegal and Mali. But ivermectin doesn't target the nearly-mature worms that cause new infections from a black fly's bite. Instead, the drug controls the symptoms until the worms eventually die out. Scientists are still searching for a compound that would block infection altogether, for example by killing the adolescent worms upon arrival.

Researchers led by Kim Janda, a chemist at the Scripps Research Institute in San Diego, California, decided to focus on an enzyme known as chitinase, which breaks down and rebuilds the O. volvulus larvae's outer casing during the final molt before adulthood. They screened 1500 drugs, looking for one that blocked the enzyme. The best candidate turned out to be a veterinary drug known as closantel, which kills liver parasites in cattle. When Janda's team cultured nearly mature O. volvulus larvae in solutions that contained various amounts of the drug for 6 days, only 1.4% of the closantel-dosed larvae had molted compared with 60% of the control group, the team reports online this week in the Proceedings of the National Academy of Sciences. If closantel has the same effect in humans, it could prevent infections from starting, says Roger Prichard, a parasitologist at McGill University in Montreal, Canada. And because it works in a completely different way from ivermectin, he says, any strains of O. volvulus that show resistance to ivermectin in the future could be treated with closantel.

Janda says that he is optimistic about working with closantel because it has already proven safe in farm animals. "That moves the drug discovery process along much more quickly." But Prichard warns that the fast track may not be so fast. Closantel isn't approved for use in all animals in all countries, including in the United States, he says. And it binds strongly to a protein found in the blood, which could lead to side effects in humans. Additionally, Janda's team would have to prove that closantel lasts long enough to provide protection between intermittent doses; one of the reasons why ivermectin works so well is that it only has to be taken once or twice a year. "It's a long way from showing an inhibition of the enzyme to actually having a drug," Prichard says. "There are substantial hurdles that would have to be overcome."

ScienceNow
March 9, 2010

Original web page at ScienceNow