Development of a Novel Synthetic Drug for Osteoporosis and Fracture Healing

Abstract

This is a progress report (year 1) for developing a novel therapeutic drug for skeletal diseases, in particular focusing on administration of salubrinal for treatment of osteoporosis and bone fracture. A formulation for salubrinal was determined and an effective dosage was identified. Using ovariectomized mice, administration of salubrinal was shown to reduce body weight and fat weight, and to prevent reduction in uterus weight and BMD/BMC. Salubrinal was also shown to inhibit osteoclast development and to stimulate osteoblast development through regulation of key transcription factors such as ATF4, NF B, and NFATc1. A pathway analysis revealed that the observed effects of salubrinal were mediated by eIF2 , p38 MAPK, and NF B pathways. Multiple invention disclosures and patents were submitted or being prepared for bone remodeling, fat metabolism, joint preservation, cancer treatment, and salubrinal coating on transplantable materials. A collaborative relationship was established with Zimmer Co. Two research abstracts were submitted, two peer-reviewed articles are in press, and one peer-reviewed research article was submitted.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2012
Accession Number
ADA570122

Entities

People

  • Hiroki Yokota

Organizations

  • Indiana University

Tags

DTIC Thesaurus Topics

  • Blood
  • Body Weight
  • Bone Diseases
  • Bone Fractures
  • Bone Marrow Cells
  • Cell Physiological Processes
  • Cells
  • Connective Tissue
  • Connective Tissue Cells
  • Diseases And Disorders
  • Macrophages
  • Materials
  • Osteoblasts
  • Osteogenesis
  • Osteoporosis
  • Proteins
  • Spine

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Regression Analysis.

Technology Areas

  • Biotechnology