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 endothelial mitogen that stimulates angiogenesis and proliferation of other cells such as fibroblasts and smooth muscle cells. After this peptide was stabilized to acid and pepsin by site-specific mutagenesis, it was tested whether bFGF might accelerate the healing of experimental duodenal ulcers. Methods: This mutein peptide (bFGF-CS23) was administered orally in comparison with cimetidine to rats with chronic duodenal ulcers previously induced by cysteamine. Results: Oral bFGF-CS23 therapy maintained for 21 days at 100 ng/100 g twice daily resulted in (1) significant acceleration of healing of duodenal ulcers, i.e., reduction of mean ulcer area by 83% in the bFGF-CS23-treated rats compared with only 61% for cimetidine therapy and 40% for untreated controls; (2) complete healing with no residual ulcer in 62% of the bFGF-CS23-treated rats compared with only 7% of untreated rats; and (3) a ninefold increase in angiogenesis in the ulcer bed compared with untreated controls. A single dose of the bFGF-CS23 mutein had no effect on gastric output of hydrochloric acid or pepsin, but daily treatment for 2 or 3 weeks 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 gastric acid.