Synthesis and characterization of a new generation of bone targeting anabolic and anti-cancer prodrugs

This project is intended to discover new drugs to treat bone diseases. Getting drugs too bone is very difficult due to poor vascularization of bones and require high doses of a potent drug which can lead to unacceptable side effects. This project intends to design, synthesize and characterize novel “bone-targeting prodrugs” to treat osteoporosis, help repair bone fractures and injuries and to treat bone cancers. These prodrugs will bind selectively to bones and then slowly release the active drugs over days and weeks so as to provide enhanced efficacy and reduced side effects.

A Novel Bone Anabolic Treatment for critical size defects in rats

Often fractures don’t heal properly or large defects must be repaired in the bone due to accidents or disease. The drugs and treatments that are currently used to repair fractures are only partially effective. Mesentech Inc has developed a new drug that has shown a strong effect on bone formation in rats. In this project, we will test the effect of this drug in a rat model of normal healing and challenging healing. We will assess the effect of this drug, to accelerate normal healing and enhance challenging healing. We expect that the new drug will make the bones heal faster and better.

Synthesis and characterization of a new generation of bone targeting anabolic prodrugs - Year two

Prostaglandin E2 stimulates bone formation in vivo and exerts its effects through the EP4 receptor. Unfortunately prostaglandin E2 and agonists for the EP4 receptor also cause unacceptable systemic side effects which have limited their clinical use as anabolic agents. We developed novel bone-targeting prodrugs that can deliver EP4 agonists selectively to bone and liberate active drug slowly in situ to effect bone formation while avoiding the side effects.

A Novel Bone Anabolic Treatment in Mouse Models of Pediatric Bone Fragility Disorders

Children that break their bones repeatedly often have genetic conditions that either affect bones directly or indirectly. The drugs that are currently used to decrease the number of fractures in children are only partially effective. Mesentech Inc. has developed a new drug that has shown a strong effect on bone formation in rats. In this project, we will test the effect of this drug in mouse models of a condition that affects bone directly (osteogenesis imperfecta) and a condition that affects bone indirectly (Duchenne Musclar Dystrophy).

Synthesis and characterization of a new generation of bone targeting anabolic prodrugs

Prostaglandin E2 stimulates bone formation in vivo and exerts its effects through the EP4 receptor. Unfortunately prostaglandin E2 and agonists for the EP4 receptor also cause unacceptable systemic side effects which have limited their clinical use as anabolic agents. We developed novel bone-targeting prodrugs that can deliver EP4 agonists selectively to bone and liberate active drug slowly in situ to effect bone formation while avoiding the side effects.

A Novel Bone Anabolic Treatment in a Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a heritable disorder that causes bone fractures. The drugs that are used at present help to decrease the number of fractures by about half, but most people with OI have many fractures despite receiving currently available treatments. Mesentech Inc has developed a new drug that has shown a strong effect on bone formation in rats. In this project, we will test the effect of this drug in a mouse model of OI. The new drug will be injected three times per week during a period of four weeks and the effect on bone strength will be assessed.