Gene silencing may save monkeys from Ebola

Reuters, May 27, 2010

Researchers say it may be best way to treat lethal virus.

A gene silencing approach can save monkeys from high doses of the most lethal strain of Ebola virus in what researchers call the most viable route yet to treating the deadly and frightening infection.

They used small interfering RNAs or siRNAs, a new technology being developed by a number of companies, to hold the virus at bay for a week until the immune system could take over.

U.S. government researchers and a small Canadian biotech company, Tekmira Pharmaceuticals, worked together to develop the new approach, described in the Lancet medical journal on Thursday.

"The delivery system is the real key," said Thomas Geisbert of Boston University School of Medicine, who did some of the work while at the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland.

Ebola viruses are a family of viruses that can often cause very serious hemorrhagic fevers. They have caused dozens of frightening and deadly outbreaks across Africa and threaten endangered gorilla populations as well as people.

There is no treatment and no vaccine against Ebola, which passes via close personal contact.

The siRNAs are little stretches of genetic material that can block the action of a specific gene. This particular one attaches to three different areas on the Ebola virus, preventing it from replicating.

Geisbert's team worked with a strain called Zaire that comes from the Democratic Republic of Congo and kills up to 90 percent of those infected.

"We have just had very difficult times developing treatments — antivirals or just any kind of a strategy," Geisbert said in a telephone interview.

"It's been a very tough nut to crack."

The team has announced a number of near-successes, most recently a vaccine that provided partial protection in monkeys in 2006. Then Geisbert got a call from Ian MacLachlan at Tekmira.

The methodology MacLachlan described sounded promising, so they teamed up.

Tests in guinea pigs suggested the siRNAs delivered in little lipid particles would work. But to get Ebola to sicken rodents requires changing it substantially from the strain that attacks people and monkeys, Geisbert said.

Tests in four rhesus monkeys showed that seven daily injections cured 100 percent of them. And Geisbert said the researchers gave the monkeys an extremely high dose of Ebola.

The treatment holds the virus in check while the immune system gears up to fight it, Geisbert said. "There is a critical threshold for virus load and if you go over that, you die," he said.

"This drug is knocking down enough of the virus so it tips the balance."

Now the company and researchers are seeking U.S. federal funding to continue their work, Geisbert said. For new drugs to treat lethal infections, the Food and Drug Administration requires proof that the treatment does not hurt people and is effective in at least two animal species.

Tekmira has deals with a number of pharmaceutical companies, including Bristol-Myers Squibb and Pfizer.

Last week a team at the National Institutes of Health reported they had developed a vaccine that protects monkeys against several strains of Ebola.