Liposome researchers seek to stop bird flu before it takes flight

Mar. 27, 2006 – A small band of researchers scattered around the country from East Tennessee State University to Harvard’s Brigham and Women’s Hospital are about to test a new, nanotech approach to heading off a potential bird flu pandemic.

The scientists are developing liposomes, fatty globules used as a tiny drug delivery device, which contain a mix of antioxidants and anti-viral drugs. The researchers believe that these liposomes, which can be reduced to a size as small as 25 to 50 nanometers, can cripple the lethal chain reaction that allows a virus to replicate, saving the patient.

By delivering a mix of a typical anti-viral agent along with antioxidants, “you are able to decrease the viral replication … of the cell,” says Milton Smith, president of Amaox.

Amaox dates back to 1992, when a group of researchers set out to study the therapeutic role of liposomes. Now, the National Institutes of Health is funding an upcoming trial of the experimental bird flu therapy at the University of Utah to determine if it should go on to animal and later human trials. Much of the team’s work to date has been sponsored by the Department of Defense, which has been interested in using therapeutic liposomes to guard against mustard gas and more recently anthrax.

“When we think of antioxidants, we think of taking them by mouth,” says Smith. “People think of them as vitamins.” But when you use liposomes as tiny delivery vehicles, then therapies can be delivered through a topical application, as an injection or inhaled when aerosolized. And by changing the way the therapy is delivered, researchers say they can increase the absorption level of the therapy and change the therapeutic quality of the drug. Taking antioxidants orally, or through the gut, limits their absorption level.

“We know that the viral infection of the lung in general produces inflammation,” says Bill Stone of the James H. Quillen College of Medicine in Johnson City, Tenn. Stone initiated much of the work that is about to be tested. “It’s always accompanied by oxidative stress. We know that these viruses use oxidative stress to aid in replication. The oxidative stress component becomes so large as to cause pathology. And we think that’s what is going on with bird flu. SARS would be a similar kind of scenario.”

Stone’s theory is that you can provide water and lipid soluble antioxidants directly into the lung through an aerosolized therapy. Those antioxidants, particularly glutathione and vitamin E, block the ability of the virus to enter the cells.

If they’re right, it could provide a generic approach to combating bird flu, rather than the hit-or-miss strategy involved when trying to develop a vaccine for the kind of moving target a swiftly mutating virus can become.

“When you make a vaccine,” says Stone, “you have to inject an antigen for a specific strain. If you miss the strain, then you’re done for.”

The researchers believe that by targeting the body’s inflammatory response to a viral infection, they can deliver a therapy that would have broad application against all strains of the H5N1 strain that has been raising fears and sparking headlines around the world.

Smith emphasizes that a virtual network of scientists has been working to advance the project. Those scientists also include Ken Alibek, formerly a scientist with the Soviet biological weapons program, Keith Crawford at Brigham and Women’s Hospital and Peter Ward at the University of Michigan.

Liposomes are rarely used in medicine, but are not unheard of. Researchers trying to modulate the side effects of the powerful breast cancer chemotherapy Adriamycin made a new variety of it called Doxil that is carried by liposomes. The newly constituted drug is absorbed more slowly, maintaining its effectiveness against the cancer while, hopefully, blunting adverse effects. Researchers at Case Western Reserve University and Copernicus Therapeutics have also developed liposomes 25 nanometers across that carry therapeutic DNA, small enough to pass through nuclear pores in order to treat cystic fibrosis.

Once you become accomplished at working with liposomes, says Stone, it actually can go quite smoothly.

“It’s like playing the piano,” says Stone. “It looks easy when you’ve seen it done right.”

In a perfect world, says Smith, it would be possible to get results from the first in vitro — or test tube — trial in a matter of weeks. With more backing from the NIH, that would allow researchers to tackle animal studies in a matter of months. And in the event of an actual bird flu pandemic, the normal rules of drug development — which often requires years of careful safety and efficacy studies — could be suspended. Theoretically, says Smith, a therapy could be approved in less than two years.

“If bird flu becomes a true pandemic,” says Smith. “Lots of things change. If you have thousands of people dying, I don’t think the FDA is going to go thru the usual due processes.”


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