Heart failure mouse model feasible as testing of potential new drug candidates, test model for serious heart failure side effects and research in mechanisms of heart failure including compensatory mechanisms.

The present license opportunity concerns a heart failure mouse model based on inducible disruption of the Serca2 gene in the heart of adult mice. Heart selective disruption of the Serca2 gene is initiated through administration of tamoxifen. Serca2 KO mice live for additional 7 weeks after Serca2 disruption due to compensatory mechanisms that prevent major cardiac dysfunction.  This time frame allows testing of the potential of new drug candidates in the treatment of heart failure. In addition, Serca2 KO mice holds promise as a test model for serious heart failure side effects, possibly including heart failure side effects similar to those associated with drugs like Avandia and Vioxx.

SERCA2 is an ATP driven Ca2+ pump that transport Ca2+ into the sarcoplasmic reticulum in heart muscle cells, thereby refilling the intracellular Ca2+ store necessary for the contractile function. Reduced SERCA2 activity has been linked to heart failure and Serca2 gene systemic homozygous knockout is early embryonic lethal.

Applications:

Serca2 KO mice have potential for use in

1) Heart protection: Discovery of drugs that protects against heart failure

2) Side effects: Test drugs for adverse induction of heart failure

3) Research in mechanisms of heart failure including compensatory mechanisms

Key publications:

1) Andersson,KB. et al, Mice carrying a conditional Serca2flox allele for the generation of Ca2+ handling-deficient mouse models, Cell Calcium (2009) doi:10.1016/j.ceca.2009.07.2004

2) Andersson KB. et al, Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 gene, J Mol Cell Cardiol. (2009) doi:10.1016/j.yjmcc.2009.03.013

Early Stage

Patent:

WO 2005/063007

EP 1 699 289 B1

US 2009/0235367

We seek partners that through collaboration will advance the use of the Serca2 KO model in:

1) Discovery and development of heart failure drugs

2) Studies of heart failure side effects that can be associated with new drug candidates