FSH Receptor Antisense Strategy for Contraception

DESCRIPTION (Scanned from the applicant's description): A new form of chemical contraceptive that has greater ease of use, more prolonged actions and a different profile of side effects than existing steroidal contraceptives would be welcomed by many women. A compound that specifically and reversibly inhibits development of ovarian follicles would be an ideal and radically different contraceptive. A specific inhibitor of follicle-stimulating hormone receptor (FSHR) synthesis is expected to be such a compound. The FSHR protein is required for ovarian follicular development and is present in ovarian follicular granulosa cells but not in non-reproductive tissues. The collaborator's laboratory has demonstrated that this compound inhibits synthesis of the FSHR in vitro. The goal of this six-month Phase I feasibility project is to determine if a phosphorothioated 18-mer antisense oligodeoxynucleotide (ODN) reversibly and specifically blocks follicular development in a mammalian species (rat) in a dose-dependent manner. The goal of the Phase II project will be to establish and refine the pharmaceutical and toxicological properties of the ODN in a primate species using a biodegradable, sustained-release, long acting, and injectable microsphere formulation of the compound. The long-term objective is to develop an FSHR antisense ODN as a contraceptive that would transiently block ovarian follicular development in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE