Gene Therapy Emerges as a Potentially New Tool in Wound Healing for …



Gene Therapy Emerges as a Potentially New Tool in Wound Healing for People with Vascular Disease: The LEGenD-1 Trial

Summary: The LEGenD-1 trial, published in Circulation: Cardiovascular Interventions, demonstrates that gene therapy using AMG0001 (a plasmid encoding hepatocyte growth factor) can accelerate wound healing in patients with chronic limb-threatening ischemia (CLTI) and neuroischemic ulcers. This phase II, double-blind, randomized, placebo-controlled study involved 75 participants across 22 U.S. sites, where intramuscular injections were administered along a target artery path. Results showed a significant reduction in median time to healing (84 days vs. 280 days for placebo) and higher complete healing rates at 6 and 12 months. The therapy promotes therapeutic angiogenesis and microvascular perfusion, offering a potential complement to revascularization for patients in a therapeutic gap, with balanced safety across groups.

Key Highlights:

  • AMG0001 gene therapy shortened median healing time to 84 days compared to 280 days for placebo (P=0.007).
  • Complete ulcer healing rates were 63.3% at 6 months and 77.6% at 12 months for AMG0001, versus 38.5% and 46.2% for placebo.
  • The study targeted patients with CLTI and neuroischemic ulcers, focusing on earlier-stage intervention beyond revascularization.
  • Therapy involves intramuscular delivery of hepatocyte growth factor plasmid to promote angiogenesis and improve microcirculation.
  • Adverse events were similar across groups, with no procedure-related influences on outcomes.

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Keywords: gene therapy, wound healing, diabetic ulcers, CLTI, therapeutic angiogenesis