Investigating In Vivo Efficacy of Novel ALN-EP4a Conjugate Drugs for the Treatment of Post-menopausal Osteoporosis
Year: 2014
Type: dissertation
Abstract: Current treatments for post-menopausal osteoporosis are mainly anti-resorptive, which decrease osteoclastic bone resorption but show little bone-building effects to reverse bone loss. The current study employs a conjugate approach in which an anabolic agent (EP4 receptor agonist) is covalently linked to an anti-resorptive agent (alendronate) to create two novel conjugate drugs: C1 and C2. The rationale is that when administered systemically, C1 and C2 will be target delivered to bone through alendronate's ability to bind to bone mineral, thereby decreasing side effects associated with systemic administration of the EP4 agonist. This study investigated the in vivo efficacy of the C1 and C2 conjugates for the treatment of post-menopausal osteoporosis in a curative experiment using the ovariectomized rat model. Results showed that the C1 conjugate dose-dependently stimulated new bone formation in both cortical and trabecular bone, while the anabolic effects of the C2 conjugates were not observed in any skeletal sites.
Source: TSpace (University of Toronto)
Author: Sally Hu
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Osteoporosis Canada
OpenAlex ID: W2728004259