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New therapy for heart failure

15.10.2008
During heart failure the body reacts to the production of the hormone aldosterone. Too much aldosterone can stiffen and damage the muscles of the heart.

Dutch researcher Luc Roumen has optimised compounds that inhibit the production of this hormone and looked at their optimum dosage. The compounds were manufactured by the companies Schering-Plough and SyMO-Chem BV and a drug patent has been applied for.

Luc Roumen has developed a new therapy for the prevention of heart failure. The idea is to administer a drug that blocks the enzyme responsible for the production of aldosterone, namely cytochrome P450 11B2. The related enzyme 11B1 is involved in the production of other important hormones. Roumen searched for a highly selective drug that would only block 11B2, but not 11B1, to ensure a minimum of side effects when the drug is administered.

Computer simulation
Roumen examined the three-dimensional structure of both enzymes using computer simulations and was able to analyse the dynamic behaviour of the enzymes and a number of candidate drugs. This provided valuable information about the interactions preferred by the 11B2 enzyme. By optimising the interactions between the enzyme and a potential drug it was then possible to develop a number of very active and selective compounds. These can later be used as medicines.
Patent
The compounds developed were synthesised by the companies Schering-Plough (formerly Organon BV) and SyMO-Chem BV. The potential of the compounds was tested on cell cultures and rat models by Maastricht University. This collaboration resulted in valuable feedback, which could be used for verification of the computer models. A patent application has been made for a drug that reacted positively both in cell culture and in the rat models. The results are being documented by Maastricht University and Schering-Plough.

Kim van den Wijngaard | alfa
Further information:
http://www.nwo.nl/nwohome.nsf/pages/NWOA_7JUHDW_Eng

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