Drugs block Ebola, Marburg viruses in tests
Synthetic nucleotides injected into monkeys can block the replication of Ebola and Marburg viruses, suggesting it eventually may be possible to protect humans against these deadly bioterrorism agents, researchers said Sunday.
The monkeys get very sick, but most of them survive. The agents, called morpholino oligomers, are the first drugs approved by the Food and Drug Administration to go into clinical trials against the viruses — although those trials will, at least initially, be conducted in primates, not humans.
The results are “a potentially important proof of concept but still a long way from a product that can be used with confidence against human infections,” said virologist Alan L. Schmaljohn of the University of Maryland School of Medicine, who was not involved in the research.
Schmaljohn cautioned that the drugs were given within an hour after infection and that they could be much less effective later in the course of the disease or against a more aggressive strain of the viruses.
Nonetheless, the experimental drugs represent the first ray of hope against two viruses that are extremely difficult to deal with in natural outbreaks and that keep bioterrorism experts awake at night worrying about their potential use by unprincipled attackers.
Ebola and Marburg are both members of the filovirus family, long threads of RNA that infect humans and other primates, causing hemorrhagic fever and, almost inevitably, death. Although researchers have been working frantically to develop drugs to treat infections, none has yet reached the stage of clinical testing.
The morpholino oligomers are a new class of drugs in a family of what is known as antisense nucleotides. Antisense nucleotides are designed to bind tightly to specific areas of viral messenger RNA, blocking replication. Such compounds already are being used to treat certain types of cancer and cytomegalovirus infections, and they are being tested against HIV. The morpholino oligomers, developed by AVI BioPharma of Washington, D.C., have specialized attachments that stabilize the nucleotides and make them more effective.
The genesis for the studies came in February 2004 when a technician at the U.S. Army Medical Research Institute of Infectious Diseases in Ft. Detrick, Md., accidentally stuck her thumb while working on mice infected with the Ebola virus. She was quickly placed in what researchers there called the “slammer,” a maximum-containment isolation unit.
Coincidentally, Dr. Patrick Iversen from AVI had delivered a lecture on campus that day about the use of antisense molecules against viruses. He volunteered to design and synthesize molecules to treat the technician if the need arose. The technician was not infected, but the research led to the report Sunday in the journal Nature Medicine.
Virologist Travis K. Warren of the Army research institute and his colleagues studied one compound, called AVI-6002, in rhesus monkeys infected with the Ebola virus. They found that 60% of the monkeys given a sufficient dose survived the infection, but all who received no drug died.
Separately, they treated 13 cynomolgus monkeys infected with Marburg virus with a second compound, AVI-6003, directed against that virus. All 13 survived. Treating monkeys infected with Ebola with the drug for Marburg produced no results, and vice versa, indicating that the treatment was highly specific.
Because clinical trials cannot be conducted ethically in humans, the FDA permits such drugs to be tested in primates, and the group will soon begin such tests. If they prove successful, the drugs will then be tried when outbreaks of infection occur in Africa.
Warren said the approach could be used to treat a variety of other infectious diseases and inherited problems. “Any disorder that involves a genetic problem can potentially be treated,” he said.
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