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Anti-Cancer Drugs May Improve Survival Rates from Biological Attacks


25 November 2004

In the aftermath of the September 11, 2001 terrorist attacks, the United States implemented a program to stockpile drugs, vaccines and other treatments for pathogens that might be used in a possible biological attack. But scientists warn that even the most meticulously-crafted and perfectly-executed emergency response plan may not be enough to prevent losses of life in the event of an attack, given the limited efficacy of existing drug treatments for pathogens such as anthrax. What can be done to improve survival rates? That topic was explored at a recent conference in Washington.

Svetlana Hopkins, a researcher at the Virginia-based National Center for Biodefense, says the quest to save lives after a biological attack with agents such as anthrax is a race against time.

"All that we have against anthrax infections is antibiotics. With such an aggressive disease such as anthrax, we have literally hours to treat people," she said.

Ms. Hopkins says, when antibiotics are administered 24 hours after exposure to anthrax, the survival rate is about 50 percent. It drops to near zero between 48 and 72 hours.

In 2001 anthrax attacks through the mail in the United States left five people dead and 17 gravely ill.  Despite intensive investigations, no one has been arrested for the crimes.

The problem for policy-makers, emergency responders and healthcare professionals is that people could be exposed to anthrax and not even realize it until they fall ill, seek medical assistance and get a diagnosis. By then, according to Ms. Hopkins, it may be too late.

"They usually will come to the hospital a day later, two days later or three days later, meaning that we need a therapy for late-stage anthrax infection," she noted.  "We [researchers] were thinking that maybe we should look to [drug] 'cocktails,' mixtures of two or three components that compliment each other. We were looking for synergy."

Svetlana Hopkins thinks she has found at least some of the components for a 'cocktail' in protease inhibitors, a class of drugs used to treat certain forms of cancer as well as the HIV virus. Protease inhibitors disrupt specific enzymes in cells. In cancer patients, they work to block enzymes associated with the growth of tumors. In pathogens, they work to block the reproduction of specific viruses and bacteria.

Ms. Hopkins says, of five protease inhibitors she tested on laboratory mice that had been exposed to anthrax, none cured the disease on their own. But three of the five showed remarkable results when paired with antibiotics recommended for anthrax treatment: ciprofloxacin and doxycycline.

Ms. Hopkins described one such pairing: the protease inhibitor known as disulfiram with the antibiotic doxycycline.

"We started to treat our animals 48 hours after infection. And here were absolutely miraculous results," she noted.  "With doxycycline alone: 30 percent survival. The mixture gave us 60 percent [survival]. And at 48 hours [after infection], you would have to see those animals. They were absolutely sick. It was very hard to believe they could recover."

If that result were to hold true for humans, a 60 percent survival rate two days after infection would constitute a significant improvement over current prognoses for anthrax cases.

Ms. Hopkins presented her findings at a conference sponsored by the National Center for Biodefense, located at George Mason University. The goal of the conference was to bring together biodefense researchers with colleagues in other fields of medicine, whose expertise might contribute to the goal of better protecting the United States from biological attack.

The National Center for Biodefense is just two years old, launched in the aftermath of the September 11, 2001 attacks. The center's director for education, Ken Alibek, once served as first deputy chief of the former-Soviet Union's offensive biological weapons program. Mr. Alibek says research into pathogens such as smallpox and anthrax has gained new importance in an era of international terrorism.

"Historically, the field of cancer research and biodefense research were divided," she said.  "Three years ago, nobody would ever have thought discussed the possibility of using some methodologies, some drugs in the field of cancer research in biodefense research, and vice-versa."

Mr. Alibek hails cooperation across scientific fields, but notes that no fail-safe cures have been found for any of the pathogens believed most likely to be used in a biological attack.

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