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Possible measles drug tests well in animals

Compound saves ferrets from related virus by blocking key enzyme

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2:00pm, April 16, 2014

UNNECESSARY SUFFERING  Despite the availability of a potent vaccine, measles continues to cause outbreaks around the world due to its high transmissibility, spotty vaccine coverage in some poor countries and vaccine avoidance in wealthy ones. The infection has no effective treatment, so researchers are working to develop antivirals.

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There’s no treatment for measles, but an experimental compound might do the trick by bogging down a key viral enzyme, a study of ferrets finds. When given to animals infected by a virus similar to the one that causes measles, the compound prevented illness.

“This is still a ways away from human testing,” says Alan Hinman, a public health physician at the Task Force for Global Health, a nonprofit organization in Decatur, Ga. “But it’s exciting to see this. I think it has potential to be really useful.”

Measles is caused by a pathogen in the genus Morbillivirus. The virus relies on an enzyme called RNA polymerase to infect and spread in a host. Because mammals don’t have the same enzyme, researchers are developing experimental compounds that target that RNA polymerase. Scientists report in the April 16 Science Translational Medicine that one such compound, called ERDRP-0519, inhibits measles virus in lab tests.

Another morbillivirus causes distemper in dogs. Since that disease is uniformly lethal to ferrets, the researchers developed an oral version of ERDRP-0519 and tested it in the animals. They exposed three ferrets to the canine distemper virus and, three days later, started giving them two doses daily for two weeks. All three survived.

The compound thwarted viral replication, allowing the animals to launch a prompt immune assault on the virus. The animals’ immune systems may even retain some “memory” that would prevent distemper in the future, but this isn’t yet established, says study coauthor Richard Plemper, a virologist at Georgia State University in Atlanta.

All other ferrets exposed to the virus died within a few weeks, including nine that had been given ERDRP-0519 starting a few days before being infected. The timing is significant. Plemper says the effectiveness of the drug candidate rests in its ability to stimulate an immune response in the ferrets when the virus is already present and replicating. If the drug attenuates the virus before it gets a foothold in the animals’ bodies, as was the case for the animals receiving the compound before infection, he says, “potentially there may never be an initial strong trigger for the immune system.”

Targeting viral enzymes is a common strategy, says virologist Diane Griffin of Johns Hopkins School of Public Health. “A lot of antiviral drugs are polymerase inhibitors, but we don’t have any for measles.” She was surprised by the new results because antiviral drugs typically work when given before infection.

Plemper says that if ERDRP-0519 succeeds in further testing against measles virus and is safe in humans, it might someday work in concert with standard measles vaccination to eradicate the disease. In a measles outbreak, public health officials try to identify the “index case,” the person who introduced measles to an area, Plemper says. Health officials then can locate other people exposed by contact with the index case. Those who haven’t been vaccinated could benefit from treatment with a drug that works like ERDRP-0519 does against canine distemper, he says, limiting new cases and lessening transmission. Measles vaccination typically doesn’t work once a person is infected.

Measles kills about 1 in 1,000 people it infects. ERDRP-0519 might protect immune-compromised people who are unable to clear a measles infection or infants who are too young to get vaccinated, says Griffin. Babies typically get the first of two shots when they are 9 to 15 months old, depending on where they live.

Editor's Note: This story was updated April 21, 2014, to correct that the ferrets' doses of the experimental drug were not in pill form.

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