Development of male contraceptive through manipulation of the sperm specific protein CalphaS

This project is aimed at developing leads for male contraceptives on a collaborative basis between Spermatech AS (www.spermatech.com), the Institute of Basic Medical Sciences, UiO and the Department of Andrology, The National Hospital of Norway (Rikshospi talet). 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, in the sperm cell. We and others have shown using knock-out (KO) mice, that CalphaS regulates sperm cell motility and male fertility. This conclusion is based on to experiments performed on sperm cells isolated from CalphaS KO mice which are unable to penetrate the egg due to abrogated swimming capability. Moreover, breeding experiments with such mice demonstrate that 100 % of the CαS KO mice are infertile. Due to CalphaS unique location and function (one target, one place, one function), our discovery is rare both in a national and international perspective. Our experiments validate Calph aS as a unique molecule that can be manipulated by substances (leads) used to develop male contraceptives. Leads that target CalphaS function are expected to be used pharmacologically to regulate sperm movement without side effects. We will in this projec t develop such lead candidates. This will enable Spematech to enter into strategic partnership with "big pharma" in order to continue further down the drug development value chain into clinical trials. In order to perform the necessary analysis in lead development, will use state of the art facilities and knowledge; relevant FUGE and EMBIO platforms, and expect to receive competitive analysis, and return important know-how to the platforms. In this project novel results and ideas will benefit the group at Department of Nutrition (UoO), Department of Andrology (Rikshospitalet), Norstruct (UoT, NFR/FUGE), Biomolecular NMR platform (UoO, EMBIO), and the Biotechnology Centre of Oslo (UoO).