Therapies tested as West Nile virus looms ever larger
Once thought to be relatively benign, the West Nile virus has proved itself capable of causing permanent disability and death, killing 45 people in the U.S. so far this year -- 14 of those in California.
People severely stricken by the virus are usually treated only for signs of the infection -- fever, headaches and stiff neck or, in worst cases, encephalitis -- because there is no treatment for the virus itself. That may not always be the case. With two experimental therapies in the works, doctors ultimately may be able to reduce the virus’ lethal toll.
“A substantial number of victims have persistent neurological problems, and the fevers are becoming more severe,” says Walla Dempsey, the West Nile program officer at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. This increased severity of West Nile symptoms lends urgency to the search for treatments.
Long common in Africa, the Middle East, Asia and parts of Europe, the West Nile virus is now firmly established in the U.S. A mosquito-borne illness whose primary hosts are birds, the virus arrived in New York City in 1999 and has migrated across the country, increasing in scope and severity each year.
West Nile’s epicenter was in Colorado last year, while California and Arizona have been hardest hit this season with 796 cases and 19 fatalities, according to the latest figures from the U.S. Centers for Disease Control and Prevention in Atlanta.
Although the North American strain of West Nile is more virulent than its foreign cousins, most people who become infected with the virus have hardly any symptoms, and the vast majority of cases are never diagnosed. Because the virus attacks the brain and spinal cord, however, the worst-hit victims experience brain inflammation (encephalitis), which can cause symptoms that last a year or more. These include severe headaches, muscle weakness or paralysis, fatigue, tremors, balance problems, memory lapses and mental disorientation.
“This is a nasty encephalitis that causes serious nervous system injury, and recovery is exceedingly slow -- the nerves just don’t bounce back right away,” says Dr. Robert A. Larsen, an infectious disease specialist at USC’s Keck School of Medicine.
Two treatments in the early stages of human tests may thwart West Nile’s damage. One of them is called NeuGene, which is a synthetic compound that throws a monkey wrench into the virus’ genetic material.
Made by AVI BioPharma in Portland, Ore., the drug prevents the virus from replicating and may also reduce serious neurological problems. The compound proved safe in a 2003 pilot study on 11 patients who had brain inflammation (10 of whom received daily injections of the drug for five days while one got a placebo).
“Anecdotally, we had three patients where we saw a definite improvement, which is encouraging but not a large enough sample to make a conclusion about the drug’s efficacy,” says Pat Iverson, a molecular pharmacologist with AVI BioPharma.
The company plans to launch a larger study in the next several weeks that will involve 50 West Nile victims who are experiencing neurological problems; 40 will receive injections of the drug, while the remainder will get a placebo.
The other treatment, Omr-IgG-am, is made by Omrix, an Israeli company. It contains infection-fighting antibodies derived from Israeli blood donors who’ve been chronically exposed to the virus, which is endemic in the Middle East. The hope is this therapy will “jump-start the immune system to fend off brain inflammation,” says Larsen, who is involved in tests of this drug.
Animal studies were encouraging. In mice infected with a lethal dose of West Nile virus, up to 80% survived after receiving Omr-IgG-am. A National Institutes of Health-funded trial of this experimental therapy is now underway at 60 sites around the country, and researchers hope to enroll up to 110 patients who have encephalitis caused by West Nile virus or who are at risk of developing this severe neurological complication.
Larsen cautions: “Even if all goes well, it will be several years before either of these products are available for general use.”
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Prevention is next step; vaccine studies underway
Simply treating West Nile virus infection isn’t enough, most doctors and researchers agree. Prevention is also crucial. Two West Nile virus vaccines, currently in development, aim to stop the virus before it gets a toehold in the body.
Scientists at Acambis Inc.,
a Cambridge, Mass., biotech company, devised a vaccine in which genes of the West Nile virus are piggybacked onto a yellow fever vaccine. Both yellow fever and West Nile virus belong to a family of viruses known as flaviviruses.
“But the immune system only ‘sees’ the West Nile virus,” says Dr. Thomas P. Monath, a medical virologist with Acambis.
In a 2003 test, 15 volunteers received the hybrid vaccine while five participants got only a yellow fever vaccine. Within 21 days of being inoculated with a single dose, the 15 test subjects had West Nile-neutralizing antibodies circulating in their blood, which meant they were immune to the virus.
The company is in the midst of a double blind randomized test on 90 healthy volunteers, half of whom will get the vaccine while the remainder receive a placebo shot, and hopes to have results within the year.
A West Nile vaccine developed by government researchers takes a slightly different approach: Proteins from the West Nile virus are grafted onto a dengue virus vaccine. (The dengue virus is also part of the flavivirus family.)
In animal tests, the vaccine triggered an immune response and protected monkeys from infection. Human tests of the National Institutes of Health-devised vaccine should begin before the end of the year.
