Discovery and development of avotermin (recombinant human transforming growth factor beta 3): A new class of prophylactic therapeutic for the improvement of scarring

Abstract

Scarring in the skin following surgery or trauma may be associated with adverse aesthetic, functional, growth and psychological effects, such that both physicians and patients regard it as important to minimize the appearance of scars. The prophylactic improvement of cutaneous scar appearance represents a significant opportunity to improve the well-being of patients. Human recombinant transforming growth factor beta 3 (avotermin) is the first in a new class of therapeutic agents to address this medical need. Herein we describe scar-free healing in early embryonic development, including the identification of the cellular and molecular mechanisms underpinning the scarring process. This understanding has led to the discovery of novel therapeutics such as transforming growth factor beta 3, which can be administered to improve scar appearance in human subjects through pharmacological action. We discuss the pioneering development of transforming growth factor beta 3 in this new therapeutic area showing how it has been possible to translate preclinical concepts into clinical application, namely the improvement of scar appearance following surgery.

Fetal Skin Possesses the Ability to Regenerate Completely: Complete Regeneration of Skin

“…When rhTGF-β3 was administered in adult wounds, scars were reduced. [23][24][25] (2) Extracellular matrix Hyaluronic acid is a major component of the fetal skin matrix, 26,27 and the increase in the ratio of hyaluronic acid in fetal wounds to that in the surrounding skin was higher than in adult wounds. [27][28][29] When procedures for decomposing hyaluronic acid in fetal wounds were car- Under a microscope, the flank skin of fetal mice was wounded in utero, and was harvested 72 h later (A).…”

Regenerative Skin Wound Healing in Mammals: State-of-the-Art on Growth Factor and Stem Cell Based Treatments

“…Moreover, phase II clinical trials showed that intradermal injections of avotermin in scar revision surgery [94] and bilateral leg wounds [95] were well tolerated and resulted in significantly improved scar appearance compared to placebo. In addition, other phase II clinical trials demonstrated significant improvement in scar formation with avotermin treatment as well [96]. …”

Chemokines in Wound Healing and as Potential Therapeutic Targets for Reducing Cutaneous Scarring

“…Recombinant human TGF-b3, Avotermin, has been demonstrated to be safe and numerous double-blind, placebo-controlled prospective trials has demonstrated statistically significant improvement in scar appearance at a range of doses and dose frequencies. 186 The key to any modulation of scar formation is the coordination of numerous cellular and molecular processes. Direct cytoplasmic coupling between cells mediated by gap junctions provides a direct line for the spread of biological information within tissues.…”