ACCELERATED HEALING OF DUODENAL-ULCERS BY ORAL-ADMINISTRATION OF A MUTEIN OF BASIC FIBROBLAST GROWTH-FACTOR IN RATS

Background/Aims: Human basic fibroblast growth factor (bFGF) is an end othelial mitogen that stimulates angiogenesis and proliferation of oth er cells such as fibroblasts and smooth muscle cells. After this pepti de was stabilized to acid and pepsin by site-specific mutagenesis, it was tested whether bFGF might accelerate the healing of experimental d uodenal ulcers. Methods: This mutein peptide (bFGF-CS23) was administe red orally in comparison with cimetidine to rats with chronic duodenal ulcers previously induced by cysteamine. Results: Oral bFGF-CS23 ther apy maintained for 21 days at 100 ng/100 g twice daily resulted in (1) significant acceleration of healing of duodenal ulcers, i.e., reducti on of mean ulcer area by 83% in the bFGF-CS23-treated rats compared wi th only 61% for cimetidine therapy and 40% for untreated controls; (2) complete healing with no residual ulcer in 62% of the bFGF-CS23-treat ed rats compared with only 7% of untreated rats; and (3) a ninefold in crease in angiogenesis in the ulcer bed compared with untreated contro ls. A single dose of the bFGF-CS23 mutein had no effect on gastric out put of hydrochloric acid or pepsin, but daily treatment for 2 or 3 wee ks resulted in enhanced acid and pepsin outputs. Conclusions: Chronic duodenal ulcers can be healed rapidly by stimulating angiogenesis and other wound-healing processes in the ulcer bed without reduction of ga stric acid.