HAMBURG, Germany ¿ MediGene AG, of Martinsried, said it validated a promising new target that is involved in the development of congestive heart failure, a disease that will affect an estimated 8.5 million patients in the U.S. and Europe by 2000.

MediGene, founded in 1995, is one of Germany¿s few biopharmaceutical product companies, and concentrates on the development of new therapeutics in cancer and cardiac disease.

Three years ago the company reported the identification of some promising candidate genes responsible for the early onset of cardiomyopathies. The starting point was MediGene¿s proprietary heart EST database, a catalogue of genes expressed in healthy and diseased hearts derived from patients with detailed anamnesis and matching biographical data. Now, the first one of those genes has been validated as a very promising target, Thomas Henkel, head of cardiology at MediGene, told BioWorld International.

¿The previously unknown protein is involved in the pathological reorganization of the contractile apparatus of the heart muscle in dilated cardiomyopathy (DCM),¿ he said. DCM is a progressive degeneration of the heart muscle that eventually leads to death by congestive heart failure or arrhythmia. So far, transplantation is the only therapeutic option. The coding gene was named DCM-associated-gene-1 (DCMAG-1) and has been patented and submitted for publication.

¿With DCMAG-1, we have not only validated a target, but our whole concept of target discovery, analysis, and validation both in vivo and in vitro,¿ Henkel said. ¿After the discovery of the gene, we analyzed its function, identified the corresponding protein and were able to demonstrate that it is overregulated in patients with congestive heart failure.¿

Using slices of diseased hearts, the scientists were able to prove that production of the protein was increased in the contractile apparatus. ¿And in animal models we could demonstrate that certain hormones which induce cardiac insufficiency lead to an increased level of that protein, too,¿ Henkel said. ¿Moreover, the localization of DCMAG-1 protein correlates with the enlargement of the heart chambers. So we have a clear correlation between animal models and the human system.¿

MediGene is designing an assay to be able to search for genes and substances able to inhibit the target. ¿But this is not the end of it,¿ Henkel said. ¿We have several further genes progressing through the validation process so that we will have a sound basis to find a strategic partner for a joint development of small molecules.¿