Oregon firm tests West Nile drug.

Byline: Tim Christie The Register-Guard

CORRECTION (ran 9/10/04): Washington is the last state in the continental United States without a human case of West Nile virus. Stories published Thursday and Friday in The Register-Guard incorrectly said Oregon was the last state without a human case.

A Corvallis biotechnology firm is launching a clinical trial to test the safety and effectiveness of a drug to treat patients who become severely ill from West Nile virus.

AVI BioPharma will test its NeuGene antisense drug, called AVI-4020, to treat West Nile patients suffering serious neurological impairment.

No approved drug therapy is available for patients with the virus. Antisense drugs send little chunks of man-made DNA into the body that target and disable specific disease-causing genes, like little smart bombs.

West Nile spread quickly across the United States since it was first detected in Queens, N.Y., in 1999. Oregon remains the last state in the continental United States without a confirmed human case of West Nile, though several horses and crows were infected by mosquitos this summer.

AVI BioPharma plans to enroll 50 patients in Southern California and Arizona this fall. Forty patients will receive a daily dose of AVI-4020 for five days in addition to the standard treatment, and 10 patients will receive a placebo for five days along with the standard treatment.

Doctors will monitor the patients daily for seven to 10 days for safety and disease progression and resolution, then periodically for six months.

If the initial small trial indicates that the drug is safe and effective, then the company would most likely launch a larger trial before seeking approval from the U.S. Food and Drug Administration, company spokeswoman Wendy Carhart said.

Last fall, AVI conducted a pilot study with 10 patients at Boulder Community Hospital in Colorado. Nine received small doses of the drug for five days and one got a placebo. The pilot study found that the drug was safe in humans, and that it had reached patients' spinal fluid within five days. That indicates that the drug was crossing the blood-brain barrier - in other words, getting to where it was supposed to go in the body.

Earlier this summer, a Michigan man who became severely ill from West Nile virus was treated with AVI-4020 under what is called an emergency investigational new drug application. The man's symptoms eased within a few days, though it was not conclusive that the drug was the chief cause, infectious disease specialist Dr. Donald Batts told the Kalamazoo Gazette.

Most people who get infected with West Nile don't have symptoms, but about 20 percent develop mild, flulike symptoms. In about one case out of 30, the virus can cause life-threatening inflammation of the brain or of the membrane surrounding the brain and spinal cord.

To date this year, 1,191 human cases of West Nile virus have been reported in the United States, resulting in 30 deaths. More than one-third of reported cases, or 429 people, developed neuroinvasive disease, according to the U.S. Centers for Disease Control and Prevention.

To put the numbers in perspective, influenza kills about 36,000 Americans every year, according to the CDC.

AVI BioPharma is hoping that the trial proves its technology works, Carhart said.

"They're looking at it not as a large blockbuster market opportunity but as a way to validate their technology and address an unmet medical need," she said.

The company's antisense technology is a marriage of biology and chemistry. The synthetic compounds mirror and bind to specific genetic sequences of a disease-causing organism. Like a key in a lock, antisense compounds are designed to match up precisely with a specific gene or viral sequence, blocking the function of the target gene or virus.

Company officials say their antisense drugs can play a key role in combating other emerging infectious diseases. AVI BioPharma officials say they can produce clinical-grade anti-viral drugs to target viral pathogens within days, if necessary, to respond to public health and bioterrorism threats.