Lackluster Sepsis Drug Combats Flu In Rodents

A drug to treat sepsis that failed clinical trials might see new life as a treatment for influenza—if studies in rodents are any indicator (Nature, DOI: 10.1038/nature12118). A new approach to flu therapy would be a welcome addition to the arsenal on hand today.

Most treatments for flu go after the virus itself, but Stefanie N. Vogel of the University of Maryland, Baltimore, and coworkers are taking a different tack. “We’re targeting the host response to the virus, rather than the virus itself,” she says. Her group’s aim is to prevent the lung inflammation and damage influenza can cause.

Vogel’s team turned to eritoran, a sepsis drug candidate, because it blocks an inflammation pathway mediated by Toll-like receptor 4, a protein on certain immune-system cells. Researchers have proposed that this pathway is involved in multiple illnesses. However, in 2011 results from a late-stage clinical trial for sepsis, eritoran proved no more effective than a placebo.

The flu response, though, may be more amenable. Vogel’s team infected cotton rats, a rodent susceptible to the same seasonal flu strains as humans, and then treated the animals with eritoran or a placebo. The eritoran-treated rats had less lung damage from flu than their untreated counterparts. Eritoran also protected mice from a mouse version of flu virus. Without eritoran, only 10% of mice infected with the virus lived. With eritoran, however, as many as 90% of infected mice survived, provided researchers treated the mice soon after infection.

“It’s great to see eritoran used to help validate the involvement of Toll-like receptor 4 in flu,” says Hang (Hubert) Yin, who studies the receptors at the University of Colorado, Boulder.

He thinks the work lends additional support to the movement to find new uses for known drug compounds.

Should eritoran prove effective against flu in people, it wouldn’t be the first time a drug ineffective for sepsis has ended up being used for another disease, Vogel says. Some drugs for rheumatoid arthritis and inflammatory bowel disease also began development as sepsis treatments. Eritoran may work by mitigating an overactive immune response and thus inhibiting ensuing lung damage. “Maybe we have found a niche for eritoran,” she says, “or for drugs like it.”