Gallium nitrate enhances natural wound healing (HSS-0015)
HSS Innovation
Office of Technology Transfer,
Hospital for Special Surgery
DESCRIPTION: Gallium, a Group IIIa transitional element that as a nitrate/citrate salt is an FDA-approved therapeutic agent. In vivo, gallium mimics the actions of TGF-b. It stimulates differentiated function in fibroblasts and keratinocytes to initiate matrix formation and repair of a wounded area. Significantly enhanced epidermal re-epithelialization was associated with increases in expression of several keratinocyte integrins known to favorably alter healing.
APPLICATION: Gallium provides a novel therapeutic approach to the management of chronic as well as acute cutaneous injuries. Gallium compounds suitable for wound healing also have cosmetic and dermatologic applications. Potential applications include removing wrinkles due to aging by stimulating matrix synthesis to increase skin thickness, selectively filling skin defects due to prior injury such as acne or trauma, and treating wounds.
ADVANTAGES: As a simple inorganic compound, gallium is non-antigenic and can readily be administered topically. It can readily be maintained in sterile solutions, it is biocompatible with many compounds, can exist in many different formulations and has a prolonged shelf-life. Active gallium compounds are orders of magnitude less expensive to make and formulate than biologics, and are chemically stable for years at room temperature. The preferred method of application of gallium compounds for wound repair is topical. Prior studies with parenteral administration of an FDA-approved formulation of gallium in doses several orders of magnitude higher than those proposed for this topical application have been shown to be safe.
STAGE OF DEVELOPMENT: Extensive in vitro testing has shown a pattern of gene induction and protein synthesis in fibroblasts, osteoblasts and keratinocytes that favor tissue healing and repair. In vivo tests have been conducted in rats, dogs, pigs and monkeys. A single topical treatment with gallium accelerated the rate of re-epithelialization of partial thickness wound repair in pigs. Increased epidermal migration occurred in the absence of a significant proliferative response. Mean re-epithelialization of partial-thickness wounds created on domestic pigs was 27% higher for pigs treated with gallium nitrate as compared to the control group. An IRB-approved protocol to test the efficacy of gallium to accelerate human wound healing awaits proper funding. Multiple clinical trials are planned. Three US patents have issued. Others are under prosecution.
posted 6/15/2005
US Patents No. 5,556,645, 5,686,116, 6,165,514, and 6,287,606. Bockman et al., "Gallium nitrate increases type I collagen and fibronectin mRNA and collagen protein levels in bone and fibroblast cells." J. Cell Biochem. 1993; 52:396-403
