Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies

Ferguson, M. W. J.; Duncan, Jonathan A L; Bond, Jeremy S; Bush, James; Durani, Piyush; So, Karen; Taylor, Lloyd A.; Chantrey, Jonquille; Mason, Tracey; James, G; Laverty, Hugh; Occleston, Nick L.; Sattar, Abdul; Ludlow, A. I.; O’Kane, Sharon

doi:10.1016/s0140-6736(09)60322-6

Cited by 252 publications

(208 citation statements)

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“…On the other hand, TGF-␤3, which is present in high levels in developing embryonic skin and thus also in embryonic wounds, is known to be involved in wound healing with no scar. Therefore, recombinant human TGF-␤3 called avotermin has been developed and tested for scar formation in adults (Durani et al, 2008;Ferguson et al, 2009). Avotermin has been postulated to promote the regeneration of normal skin and to improve scar appearance by reducing the deposition of ECM components such as collagen and fibronectin and by influencing the organization of the newly deposited ECM in the wounded dermis .…”

Section: A Targeting the Synthesis Of The Extracellular Matrixmentioning

confidence: 99%

“…Which of the above agents will finally translate into clinical practice remains to be seen. However, recent results with avotermin are encouraging: in three double-blinded, placebo controlled studies, avotermin administered intradermally to both margins of skin incisions, before wounding and 24 h later, has shown an accelerated and permanent improvement in scarring without any substantial adverse events (Ferguson et al, 2009).…”

Section: A Targeting the Synthesis Of The Extracellular Matrixmentioning

confidence: 99%

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Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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Section: A Targeting the Synthesis Of The Extracellular Matrixmentioning

confidence: 99%

Section: A Targeting the Synthesis Of The Extracellular Matrixmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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“…In this study, we have used the CAR peptide to generate a CARdecorin fusion protein for targeted delivery of decorin into injured tissues. The three different isoforms of TGF-β can have opposing effects on fibrosis (5); TGF-β1 is the main scar-inducing form and TGF-β2 augments the profibrotic actions of TGF-β1, whereas TGF-β3 counteracts scar development (5,20,21). As decorin is thought to inhibit all TGF-β isoforms (22), we also studied the TGF-β inhibition profile of the CAR-targeted decorin.…”

mentioning

confidence: 99%

Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice

Järvinen

Ruoslahti

2010

Proc. Natl. Acad. Sci. U.S.A.

179

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Permanent scars form upon healing of tissue injuries such as those caused by ischemia (myocardial infarction, stroke), trauma, surgery, and inflammation. Current options in reducing scar formation are limited to local intervention. We have designed a systemically administered, target-seeking biotherapeutic for scar prevention. It consists of a vascular targeting peptide that specifically recognizes angiogenic blood vessels and extravasates into sites of injury, fused with a therapeutic molecule, decorin. Decorin prevents tissue fibrosis and promotes tissue regeneration by inhibiting TGF-β activity and by other regulatory activities. The decorin-targeting peptide fusion protein had substantially increased neutralizing activity against TGF-β1 in vitro compared with untargeted decorin. In vivo, the fusion protein selectively accumulated in wounds, and promoted wound healing and suppressed scar formation at doses where nontargeted decorin was inactive. These results show that selective targeting yields a tissue-healing and scar-reducing compound with enhanced specificity and potency. This approach may help make reducing scar formation by systemic drug delivery a feasible option for surgery and for the treatment of pathological processes in which scar formation is a problem.

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“…Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, Phase I/II studies Physicians and their patients are highly concerned about scarring, even in relatively minor scars [8]. Although various treatments have been evaluated, no single therapy has been adopted as a universally accepted standard of care for treatment of scars.…”

Section: Retaining System Of the Face: Histological Evaluation Of Thementioning

confidence: 99%