Optimization of Fibroblast Growth Factor-1 as an Anabolic Agent for Osteoporosis
Annual rept. 20 Sep 1996-19 Sep 1997
AMERICAN RED CROSS ROCKVILLE MD
Pagination or Media Count:
The long term goal of this research program is to develop fibroblast growth factor-i 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 are 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 effects. 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 data obtained to date indicate that the proposed research plan was realistic and rational. We have generated five different FUF- 1 variants and shown utility of some of these variants in vivo. The results of the in vivo and in vitro studies indicate a logical progression towards optimizing the anabolic activity of the protein for bone will be possible. The cys-free mutant of FGF- 1 has been studied extensively and this construct is likely to become the parent protein to which other mutations will be incorporated.
- Anatomy and Physiology