Development and testing of drug candidates for male contraceptives

This project is a drug discovery R&D effort aiming at developing and testing drug candidates for male contraceptives. The project will be performed in a collaboration between Spermatech AS, the University of Oslo, the Norwegian Biotechnology Center, the U niversity of Tromsø, and the National Hospital of Norway. We have identified and characterized the function of the gene and the protein for CalphaS. CalphaS is only expressed (identified) one place in the body, namely the sperm cell. We and others have s hown using knock-out (KO) mice that CalphaS regulates sperm cell motility and male fertility. This conclusion is based on two experiments performed on sperm cells isolated from CalphaS KO mice which are unable to penetrate the egg due to abrogated swimmin g capability. Moreover, breeding experiments with such mice demonstrate that they are 100 % infertile. Our experiments validate CalphaS as a unique molecule that can be manipulated by substances (leads) that can be used to develop male contraceptives. Du e to CalphaS unique location (also within the sperm cell) and function (one target, one place, one function) our discovery is rare both in a national and international perspective. Substances that can target CalphaS function are expected to be used pharma cologically to regulate sperm movement without side effects. The main goal in this project is to identify and verify small molecular substances as drug candidates, that regulate the CalfaS protein. This will be done by computerbased drug design, high thr oughput screening (HTS) and testing in our assays. Verified drug candidates will set the basis for the development of male contraceptives for man in collaboration with international pharmaceutical enterprises.