The Effect of a Connexin43-Based Peptide on the Healing of Chronic Venous Leg Ulcers

A Multicenter, Randomized Trial

Gautam S. Ghatnekar, Christina L. Grek, David G Armstrong, Sanjay C. Desai, Robert G. Gourdie

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways.

Original languageEnglish (US)
Pages (from-to)289-298
Number of pages10
JournalJournal of Investigative Dermatology
Volume135
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Varicose Ulcer
Connexin 43
Leg Ulcer
Multicenter Studies
Ulcer
Standard of Care
Peptides
Compression Bandages
Wounds and Injuries
Connexins
Fibroblasts
Therapeutics
Moisture
Gels
Wound Healing
India
Clinical Trials
Skin

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The Effect of a Connexin43-Based Peptide on the Healing of Chronic Venous Leg Ulcers : A Multicenter, Randomized Trial. / Ghatnekar, Gautam S.; Grek, Christina L.; Armstrong, David G; Desai, Sanjay C.; Gourdie, Robert G.

In: Journal of Investigative Dermatology, Vol. 135, No. 1, 01.01.2015, p. 289-298.

Research output: Contribution to journalArticle

Ghatnekar, Gautam S. ; Grek, Christina L. ; Armstrong, David G ; Desai, Sanjay C. ; Gourdie, Robert G. / The Effect of a Connexin43-Based Peptide on the Healing of Chronic Venous Leg Ulcers : A Multicenter, Randomized Trial. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 1. pp. 289-298.
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