Parasitic nematodes are responsible for a number of severe diseases in humans, animals and plants. Approximately $600 million is spent each year on drugs to treat nematode infections in animals. These drugs are not completely effective so the discovery of new therapies and drug targets is of paramount importance. Recently we employed a novel bioinformatics approach to identify valid drug targets in nematodes that are absent from mammals. A particularly promising enzyme target has been discovered and validated which merits further development. Phase I of this project led to the successful development of a target-based screening system and assays to measure enzyme activity and inhibition. Pilot screening of various libraries has commenced and hits have been obtained which are being characterized further. With Phase II funding, we will perform more extensive screening with the goal of identifying potent inhibitors of enzyme activity. The hits will be evaluated further for broad-spectrum enzyme inhibitory activity by measuring their effects on the target isolated from other nematodes. To determine target specificity, hits will be tested in other assays involving distantly related enzymes. Non-specific cytotoxicity will be determined using mammalian cell lines. The most promising inhibitors will be evaluated for nematocidal and anti-bacterial activity in various in vitro and in vivo systems. Active compounds may also be tested for their effects on other organisms that possess the target. This will provide the basis for discovering a new class of drugs that may be used in veterinary and human medicine. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AI061865-03
Application #
7172951
Study Section
Special Emphasis Panel (ZRG1-IDM-B (12))
Program Officer
Rogers, Martin J
Project Start
2004-07-01
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2009-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$326,440
Indirect Cost
Name
New England Biolabs, Inc.
Department
Type
DUNS #
066605403
City
Ipswich
State
MA
Country
United States
Zip Code
01938