New Skin Wound-Healing Compound Shows Promise in First Clinical Trial
ACT1 peptide stops immune response
According to the results of a recent phase II study published in the Journal of Investigative Dermatology, a new wound-healing peptide, ACT1, has demonstrated the ability to heal venous leg ulcers twice as quickly as the current standard of care.
Venous leg ulcers result from too much pressure in the leg’s veins, causing the tissues to break down from the inside out. It is a particular problem in the elderly and can lead to painful and hard-to-heal open wounds.
“One of the problems you have with chronic wounds, like venous leg ulcers, is that the wounds get stuck in an inflammatory phase, and they won’t close,” said senior author Dr. Robert Gourdie, the compound’s developer. “After doing some preliminary studies, we saw that treatment with ACT1 encouraged wound closure much more quickly than normal.”
In the clinical trial, the participants had ulcers with an average circumference of approximately 3.5 cm. Their ulcers had been open for about 17 months. Subjects treated with ACT1 plus compression-bandage therapy experienced significantly better results compared with those who used only compression bandages. In the ACT1 group, 79% of the ulcers were closed after 12 weeks of treatment, compared with 36% of the ulcers in the control group.
Gourdie and his colleagues initially developed ACT1 in his laboratory at the Medical University of South Carolina while studying how to improve electrical communication between heart-muscle cells. Gourdie is now a scientist at the Virginia Tech Carilion Research Institute.
ACT1 works by binding to the ZO1 protein, thereby preventing it from connecting to another protein known as connexin 43. It is the first connexin-targeting drug that has successfully completed a clinical trial, according to Gourdie.
Healthy cells have canals known as hemichannels that are normally sealed shut within their membranes. When the cell undergoes trauma, such as a heart attack, the hemichannels open, allowing the cell’s insides to spill to the outside — a major signal of trouble to other systems in the body.
“The opening of the hemichannels causes white blood cells, a prime inflammatory cell that kicks off the immune response, to descend on the injury like a pack of wolves to protect the rest of body,” Gourdie said.
Injuries don’t have just the one trauma; they also have to handle a second response. Once the hemichannels open, the injury area swells; scar tissue forms; and it takes longer for the injury to heal. When ACT1 inhibits connexin 43 from binding to ZO1, it snaps the hemichannels closed.
“We think that by shutting the hemichannels with ACT1, we’re stopping them from triggering that immune response,” Gourdie said. “But we have more work to do to understand every piece of the process.”
Source: Virginia Tech; August 21, 2014.