RATIONALE FOR BASIC FGF IN WOUND HEALING AND REVIEW OF THERAPEUTIC APPLICATIONS

*Luca Spaccapelo, MD

ABSTRACT

Several scientific groups are evaluating the opportunity to develop basic fibroblast growth factor (bFGF) for ophthalmic and other uses. While a number of clinical studies with growth factors have been conducted in the United States and Europe, most experience of bFGF appears to derive from studies in Japan and China, where products based on bFGF have been marketed for more than a decade, primarily for cutaneous wound healing, but also involving studies in bone regrowth and periodontal procedures; relatively less data are available in the open literature regarding ophthalmological use in humans. In Asia, many cytokines are currently under development, including TGF-, EGF, and IGF-1 aside from the already marketed Fiblast Spray® (Japan) and the Beifushu series from Essex Biotechnology Ltd (China). A general concern with all growth factor-based therapies is promotion of tumour growth; in animal models, bFGF injected at the tumour inoculation site induce marked tumour growth and lymph node metastasis, correlating with an increase in neovascularization in the host stroma. Increased mortality from malignancies has been reported in patients treated with becaplermin, also involving tumours distant from the site of application. These concerns are likely to be more pronounced in relation to systemic treatment approaches (i.e. cardiovascular, bone fractures), even though the permanence of systemically administered FGF is likely to be short in the circulation. Specifically in the case of ophthalmological use, another general concern of growth factor therapy is corneal neovascularisation, which would represent an absolute contraindication of FGF therapy for corneal lesions. Against this background, it may be concluded that bFGF may have therapeutic utility in cutaneous wound healing and plastic surgery, while the ophthalmic utility appears less substantiated by published data, where no specific advantages of bFGF treatment have appeared as compared to current standard of care. The concerns regarding tumour promotion likely represent a significant hurdle, and may preclude systemic use (cardiovascular; bone healing) until large-scale and long-term safety studies have been completed to allow a more stringent risk/benefit analysis.

Keywords: fibroblast growth factor, wound healing, corneal neovascularisation, cytokines, becaplermin.