Biodefense toxins such as ricin, botulinum neurotoxins, and Shiga toxin are a source of concern for terrorist attacks due to their high toxicity and the limited post-exposure treatment alternatives. Each of these protein toxins exhibits an enzymatic activity that is the basis of its toxicity. Inhalation and ingestion are the primary routes of entry for protein toxins, and once these molecules have entered the cell, treatment options are severely limited. Physical Sciences Inc. (PSI) proposes to develop highly specific binding agents that will inhibit the catalytic activity of botulinum neurotoxins (BoNT). The proposed novel therapeutics will incorporate materials and methods for efficient delivery of the agents to the cytoplasm of target cells thus reversing inhibition of neurotransmitter release. Phase I research will develop novel BoNT inhibitors and demonstrate their efficacy using both in vitro and cell-based assays. In Phase II the agents and delivery vehicles will be optimized and will be tested for their ability to prevent or reverse the effects of BoNT intoxication in live animal models. We anticipate that the proposed system will deliver sufficient quantities of therapeutic to the cytoplasm to increase the LD50 of the agents at least 10-fold and significantly reduce recovery time for BoNT exposure.

Public Health Relevance

Post-exposure treatment options for protein toxins such as ricin and botulinum are limited. This research seeks to develop post-exposure therapies for protein toxin exposure that will greatly improve survival rates. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AI075709-01A2
Application #
7611019
Study Section
Special Emphasis Panel (ZRG1-IDM-Q (10))
Program Officer
Wachtel, Marian R
Project Start
2008-08-05
Project End
2010-07-31
Budget Start
2008-08-05
Budget End
2010-07-31
Support Year
1
Fiscal Year
2008
Total Cost
$243,590
Indirect Cost
Name
Physical Sciences, Inc
Department
Type
DUNS #
073800062
City
Andover
State
MA
Country
United States
Zip Code
01810