Development of a Novel Synthetic Drug for Osteoporosis and Fracture Healing.

摘要

This is a progress report (Year 3) for the development of a novel therapeutic drug (salubrinal and guanabenz) for skeletal diseases, focusing on potential treatment of osteoporosis and bone fracture. The study in the third year was focused on the subtasks in Tasks 3, 4, and 5, using animal models and in vitro cell cultures. In vivo data supported efficacy of salubrinal and guanabenz on strengthening bone in bone necrosis (Task 3) and bone fracture (Task 4). In vitro data showed genome-wide mRNA & microRNA expression patterns in response to salubrinal and guanabenz, and they indicated novel signaling molecules involved in the responses to salubrinal and guanabenz. In Task 5, a clinical trial of guanabenz is being planned at Indiana University for cancer patients with bone metastasis who suffer from severe bone loss. The study in the fourth year will be conducted focusing on Task 4 (bone fracture using local administration of the proposed agents), together with integration of in vitro/in vivo data for a clinical trial at Indiana University.