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news.Scientists funded by the US National Institute of Allergy and Infectious Diseases have engineered a powerful anthrax toxin inhibitor that has worked well in small-scale animal tests. The scientists say the technique may also be applicable to other disease toxins.
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Led by National Institute of Allergy and Infectious Diseases (NIAID) grantees from Rensselaer Polytechnic Institute and the University of Toronto, the investigators built a fatty bubble studded with small proteins that can cling tightly to the cell membrane receptor-binding protein used by anthrax toxin to gain entry into a host cell.
The protein-spiked fatty bubble, or “functionalized liposome,” hampers a critical early step in the assembly process that anthrax toxin must undergo to become fully active. In test-tube experiments, the inhibitor, which is covered with multiple short proteins (peptides), was 10,000 times more potent than unattached peptides.
“If the effectiveness of anthrax inhibitors designed in this fashion is confirmed by additional testing, they could one day be important adjuncts to standard antibiotic therapy for the treatment of inhalation anthrax,” says NIAID director Dr Anthony Fauci. Antibiotics are used to treat anthrax, but even with such therapy, inhalation anthrax, the most severe form of the disease, has a fatality rate of 75%.
The investigators tested the anthrax inhibitor in rats. When given in relatively small doses, injection of the inhibitor at the same time as anthrax toxin prevented five out of nine rats from becoming ill. Slightly higher doses of the inhibitor prevented eight out of nine rats from being sickened by anthrax toxin. Nine additional rats were injected with anthrax toxin only. Of these, eight became gravely ill.
“This novel approach to the design of anthrax antitoxin is an important advance, not only for the value it may have in anthrax treatment, but also because this technique could be used to design better therapies for cholera and other diseases,” said National Institutes of Health (NIH) director Dr Elias Zerhouni.
Using the same technique of placing multiple peptides on a liposome, the researchers also created a polyvalent inhibitor of cholera toxin that functioned well in test-tube experiments.
In the next phase of their research, the scientists plan to test the action of their inhibitor in animals after infecting them with B. anthracis and allowing the disease process to begin. They also will evaluate the inhibitor with and without adjunct antibiotic therapy.