The effect of a connexin43-based Peptide on the healing of chronic venous leg ulcers: a multicenter, randomized trial.

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.
AuthorsGautam S Ghatnekar, Christina L Grek, David G Armstrong, Sanjay C Desai, Robert G Gourdie
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 135 Issue 1 Pg. 289-98 (Jan 2015) ISSN: 1523-1747 [Electronic] United States
PMID25072595 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Connexin 43
  • GJA1 protein, human
  • Peptides
  • Adult
  • Chronic Disease
  • Connexin 43 (chemistry, metabolism)
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Leg Ulcer (drug therapy, pathology)
  • Male
  • Middle Aged
  • Peptides (administration & dosage, adverse effects)
  • Prospective Studies
  • Protein Structure, Tertiary
  • Treatment Outcome
  • Wound Healing (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password:
Type Validation Code Shown: