Anthrax has gained notoriety in recent years as a potent agent of biological warfare. Inhalation of anthrax spores results in the release of a deadly anthrax toxin that results in severe toxic symptoms and death. Fears of anthrax as a biological agent were realized when anthrax contaminated mail resulted in several fatalities shortly after the bioterrorist attacks of September 11. This episode highlighted the shortcomings of the current treatments available for anthrax infection and accentuated the urgency to identify new and better treatments. Thus, the primary objective of our proposal is to use our unique combination high through-put screening technology to identify and evaluate novel combinations of approved drugs that will work through multi-target mechanisms to block the adverse effects of anthrax toxin. Screening with approved drugs is highly advantageous because newly identified therapeutics may be rapidly advanced to human use and, in most cases, are readily available to be used immediately """"""""off-the-shelf."""""""" The ready availability of approved therapeutics will increase the probability of survival in the event anthrax is used as a bioweapon. Most importantly, the development of new and powerful anti-toxin therapeutics will alleviate the fear and effectiveness of anthrax as an agent of biological warfare. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI061345-04
Application #
7439128
Study Section
Special Emphasis Panel (ZAI1-LR-M (M1))
Program Officer
Xu, Zuoyu
Project Start
2005-04-15
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$647,702
Indirect Cost
Name
Combinatorx, Inc.
Department
Type
DUNS #
930118349
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Newman, Zachary L; Sirianni, Nicole; Mawhinney, Christina et al. (2011) Auranofin protects against anthrax lethal toxin-induced activation of the Nlrp1b inflammasome. Antimicrob Agents Chemother 55:1028-35
Lehár, Joseph; Krueger, Andrew S; Avery, William et al. (2009) Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nat Biotechnol 27:659-66