Anti-clot treatment used against Ebola

Army tests on monkeys produce longer survival, 33 percent recovery rate


Army scientists said yesterday that they had taken an important step toward a possible treatment for the deadly Ebola virus in humans by successfully treating monkeys with the disease for the first time.

In tests of an experimental drug among a small number of monkeys that were deliberately infected with Ebola, one-third survived, the scientists reported in The Lancet medical journal.

Ebola infection, which causes severe internal bleeding, is usually 100 percent fatal among monkeys and 80 percent among humans. So a 33 percent survival rate for one of the most virulent diseases known is significant, said the authors, from the Army Medical Research Institute of Infectious Diseases at Fort Detrick, Frederick County.

The drug, which is derived from hookworms, is being tested in other studies in humans for heart disorders and appears to be safe, the authors said. But they said more research was needed before the drug, known as rNAPC2 (recombinant nematode anticoagulant protein c2), could become an accepted treatment for Ebola.

Experts not connected with the Army research expressed cautious optimism, given the paucity of treatments for Ebola and other hemorrhagic fevers.

"Obviously, this work that got a highly significant decrease in death rates needs to be pursued," said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases.

No treatment now exists for Ebola, and tests of a vaccine have just begun in humans. Though scientists have had earlier successes in treating the disease in mice and guinea pigs with antivirals, these drugs did not work in nonhuman primates.

In the new study, the scientists injected 12 rhesus macaque monkeys with Ebola virus. Beginning either immediately or 24 hours later, nine received rNAPC2 for 14 days. Three of the nine monkeys survived; death was slowed by several days in the other six. All three untreated animals died.

"Our results have great clinical implications, since our treatment approach of Ebola hemorrhagic fever targets the disease process rather than the replication of the infectious agent," the team headed by Dr. Thomas W. Geisbert reported.

Ebola usually starts with a sudden fever and flulike symptoms of malaise, muscle aches and headache, followed by vomiting, diarrhea and a rash. The virus disrupts the blood-clotting system in monkeys and humans, leading to abnormal blood clotting, then to severe bleeding and death.

White blood cells known as macrophages seem central to the process by releasing a protein called tissue factor on the surface of the cells. As blood flows, tissue factor forms clots that pave the way for the severe bleeding.

Geisbert, Dr. Peter Jahrling and other team members chose the anticoagulant rNAPC2 because they theorized it would block the harmful effects of tissue factor.

In an interview this week in Dallas, Terry M. Fredeking, a co-author and an expeditionary biologist, said he supplied the raw material that was used to recreate a protein for the new drug.

"I won't say how long it took me to persuade Peter Jahrling that spit from hookworms might be able to treat monkeys with Ebola," said Fredeking, founder and president of Antibody Systems Inc., a research company in Hurst, Texas.

Fredeking said the World Health Organization in Geneva had asked team members whether rNAPC2 might be used on an experimental basis to treat people in a current outbreak of Ebola in the Congo. That outbreak, thought to be waning, had caused 28 deaths as of Dec. 2, according to the WHO

The patent on the drug is held by Dendreon, a small Seattle biotechnology company. Stephen Keane, director of business development, said Dendreon was willing to consider letting it be tested in the Congo but had not been contacted by health officials. WHO experts on Ebola could not be reached for comment.

Ebola was discovered in 1976 in what is now Congo. The source of the virus in nature is not known. It has spread quickly in hospitals where the staff does not have the masks, gowns and other standard protective clothing needed for isolating an infected patient.

Dr. C.J. Peters, an infectious disease expert at the University of Texas Medical Branch at Galveston who has worked on Ebola, called the new results "very impressive."

He said a treatment for the Ebola virus is even more important than a vaccine, in part because many police, public health workers and others on the frontline of health crises had been reluctant to take the smallpox vaccine after it was offered by the federal government.

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