NEW YORK (Reuters Health) - ToxBlox, a recombinant form of anthrax protective antigen, protects animals from anthrax infection and death, according to data reported Sunday in Washington, DC at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), a meeting of the American Society for Microbiology.
ToxBlox is a profound dominant negative inhibitor of anthrax toxin action, Dr. Solomon Langermann from PharmAthene, Inc., in Annapolis, Maryland, noted in an interview with Reuters Health. It has potential not only as a “rescue therapy” for symptomatic anthrax infection but also as a protective recombinant anthrax vaccine.
“Once anthrax spores are taken up into the lungs, they get into certain cells where they germinate and enter the blood stream where they make a very potent toxin,” Dr. Langermann explained.
“ToxBlox is a novel therapeutic designed to block the ability of the anthrax toxin to get into cells where it has lethal effects. A lot of therapies work too late in the process when those exposed are already symptomatic and the toxic effects are pretty far along,” he added.
In an earlier proof of concept study, ToxBlox protected rats from death when injected up to 4 hours after lethal anthrax challenge. In the latest studies reported Sunday, New Zealand White rabbits were challenged subcutaneously with an atypically high dose of anthrax and then treated 30 minutes later with ToxBlox, at doses of 1.5 or 15 mg/kg QID, or vehicle control. No antibiotics were given to the animals.
Five of 6 rabbits treated with high-dose ToxBlox survived free of symptomatic anthrax infection for a period of 90 days. In contrast mean time to death in control animals and low-dose ToxBlox-treated animals was 2.5 and 4.0 days, respectively.
“These results suggest that the long-lasting protection induced by ToxBlox may not be limited to its direct antitoxin activity,” investigators write in the meeting abstract.
“We are very pleased with the results so far,” Dr. Langermann told Reuters Health. “We basically demonstrated in an appropriate animal model for anthrax challenge that the molecule works.”
“We’ve done a second animal study now, which mimics aerosol delivery and uptake into the lungs and we are planning on starting human trials in the next month,” he added.
MeSH Headings:Animal Diseases: Disease Models, Animal: Drugs, Investigational: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
