Optimization of Fibroblast Growth Factor-1 as an Anabolic Agent for Osteoporosis
Abstract
The long term goal of this research program is to develop fibroblast growth factor-i (FGF- 1) through rational protein engineering into a potent and specific anabolic agent for the treatment of osteoporosis and fracture repair. The specific aims of this research plan remain: 1) to evaluate the effects of existing mutant forms of FGF- 1 on bone cells in vitro, on bone formation in vivo, and to assess their toxicological or undesirable activities 2) to generate additional FGF- 1 mutants or chimeric proteins that are likely to exhibit enhanced anabolic activity on bone with reduced toxicological effects. During the current year of support we have made significant progress with regard to these specific aims. The most important find was the demonstration that systemic FGF- 1 could not only preserve but restore bone mass in animal models of osteoporosis. In addition, we were able to establish the fact that site-directed mutagenesis of FGF- 1 could be used to generate mutant forms of the protein with enhanced anabolic activity for bone formation and reduced toxicological effects. This is the first demonstration of the concept that formed the basis of the original specific aims.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADB246514
Entities
People
- Wilson H. Burgess
Organizations
- American Red Cross