Bearsden Bio Inc. has developed novel compounds that selectively regulate glutamate receptor subtypes. In Phase I we synthesized a large number of AMPA receptor allosteric antagonists and tested them for inhibition of APA and kainate induced calcium influx into cortical cells. We were able to group the over 50 compounds into categories and determine their structure/activity profile. We also tested the activity of some promising compounds against MES induced seizures and compared it to their sedative effect on the rotarod. Our structure activity program from Phase I produced ligands that exhibit good affinity for AMPA receptors and promising separation between the desired anticonvulsant response and the major side effect, the drop in performance on the rotarod. We continued to synthesize new analogs to better understand the structure activity relation of the compounds and we have, to date, identified several more compounds with promising in vitro activity. We are seeking Phase II funding to better understand the mechanism of action of these novel AMPA antagonists including their subtype specificity and efficacy animal models of epilepsy to determine the best compound for further development we will select an allosteric AMPA antagonist as lead candidate for the treatment of epilepsy. The preclinical studies about Phase II will include pharmacokinetics, metabolism and toxicity. At the same time we will be preparing alternative candidates for use as back-ups in the event our lead should not have the requisite properties of a clinical candidate for the treatment of epilepsy.

Proposed Commercial Applications

Not Available

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44NS036902-02A2
Application #
6293285
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (02))
Program Officer
Chen, Daofen
Project Start
1997-09-30
Project End
2003-07-31
Budget Start
2001-09-30
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$436,035
Indirect Cost
Name
Annovis, Inc.
Department
Type
DUNS #
City
Aston
State
PA
Country
United States
Zip Code
19014