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Demonstration of an in vitro test for excitotoxicity based on early response gene measurement


The objective of the project is to demonstrate the technical viability and superiority of a new in-vitro test for excitotoxicity based on early response gene measurement.
In previous EU BRIDGE and BIOTECH-1 research contracts (CT-900182 and CT 930224), some of the applicants (Partner B and 2 sub-contractors) have shown that delayed but progressively elevated c-fos mRNA expression is associated with excitotoxicity and that a ratio measurement of c-fos expression at 240/30 min after toxic insult of mouse neuronal primary cultures correlates with excitotoxic outcome. This has been shown to form the basis for a simple in-vitro assay using c-fos mRNA levels as a predictive index. This in vitro test has a significant in vivo relevance because sustained c-fos expression has been shown to be associated with neuronal apoptosis and developmental failures.
Thus we have established original and novel research results which have allowed us to develop an in vitro toxicity test for use in the screening of chemical compounds for their toxicological and pharmacological potential.
The proposal content is intended to prove the technical viability and superiority of the new test in regard to:
- reproducibility, reliability and robustness for technology transfer, - existing methods used to indicate excitotoxicity, - proving the test in comparison to other assay methods, formats and end-points, - proving the test in an industrial context.
In this manner at the end of the project we will have accumulated data on these aspects of the new test, and will have disseminated this information to an extended audience of scientists, regulatory bodies, Industry Platform, ECVAM and European Industry.
The partners in this project include the inventors, three end-users, a synthetic organic chemistry group and an experienced technology exploitation/management team as coordinator. The participation of this multi-disciplinary grouping will ensure a successful outcome of the project.

Funding Scheme

CSC - Cost-sharing contracts


Enterprise Ireland - Trading as Bioresearch Ireland
Trinity College
2 Dublin

Participants (4)

Bayer AG
Aprather Weg
42096 Wuppertal
Neurosearch A/S
26 B,smedeland
2600 Glostrup
Via Bianchi Di Sotto 55
53100 Siena
University of St Andrews
United Kingdom
Queen's Terrace
KY16 9TS St Andrews