SFU Royal Society of Canada: Seminar Series: "Development of novel strategies and anabolic agents to treat osteoporosis and bone diseases"

Abstract

Macromolecular drug targets for treatment of bone diseases are usually expressed in other tissues and modulation can lead to systemic side effects limiting dose and efficacy. Selective bone targeting of pro-drug moieties and slow local release of the active agents can overcome these side effects. Prostaglandin E2 stimulates bone growth in vivo but has a number of other undesirable effects in the body which has obviated its use for treating osteoporosis. We have developed and evaluated a number of novel technologies utilizing bone-targeting pro-drugs wherein prostaglandins (and analogs) are linked to bioactive bisphosphonates (BPs) to provide unique pro-drugs designed for delivery and slow drug release over extended time. The optimized compounds deliver and release the anabolic agent (the prostaglandin) and the bone resorption inhibitor (the BP) selectively in the bones and thus avoid the systemic side effects and showing excellent efficacy in rodent models of osteoporosis.