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-1 (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 finding was the identification and production of FGF-1 variants with enhanced anabolic activity for bone. We also identified differences in the abilities of these constructs to promote osteoblast differentiation from marrow cultures. Finally we have demonstrated for the first time the ability of an FGF-1 variant to exhibit increased activity for bone with reduced hypotensive effects relative to the wild-type protein.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB255323
Entities
People
- Wilson Burgess
Organizations
- American Red Cross