“Revolutionizing” plastic surgery scarring outcomes: AlphaCT1 may improve appearance of scars

03 Aug 2022 --- The alphaCT1 molecule may help mend the skin’s collagen matrix by changing the behavior of cells that generate scars. This is according to research from the Fralin Biomedical Research Institute at Virginia Tech College, in the US.

The research reveals that a previously unknown component (the molecule) of scar formation and the findings could and could help enhance wound healing treatments for patients undergoing surgical procedures.

Additionally, researchers note that AlphaCT1 affects wound healing by temporarily disrupting the cell signaling functions of connexin 43, a gap junction channel protein.

“This is some of the most exciting basic science research in wound healing I’ve seen in a long time,” says Kurtis Moyer, chief of plastic and reconstructive surgery for Carilion Clinic and a professor of surgery at the Virginia Tech Carilion School of Medicine.

“This shows real promise and could potentially revolutionize what we do in plastic surgery.”

According to multicenter, controlled phase II clinical trials, surgical scars treated with the alphaCT1molecule showed a long-term appearance improvement compared to control scars. This discovery may assist surgeons in improving patient outcomes.

The findings come when more than 300 million surgical procedures are carried out in the US annually, frequently leaving patients with visible scars. Therefore, researchers note that techniques that lessen scarring are highly sought.

Bringing alphaCT1 to the market
Gourdie and his lab invented the molecule a decade ago and discovered its beneficial effects on wound healing with his former postdoctoral associate, Gautam Ghatnekar. To bring alphaCT1 to market, they formed FirstString Research, a biopharmaceutical company.

The researchers explain how the alphaCT1 molecule affects the behavior of fibroblasts – the cells that produce collagen.Since 2018, the company has raised US$55 million in Series B, C and D funding. It tests the molecule in various applications, including surgical wound healing, chronic wound healing, radiation therapy and corneal tissue repair.

Additionally, alphaCT1 is currently being tested in phase III clinical trials in patients undergoing bilateral breast surgery.

“These findings validate that the molecule’s mechanism is playing out as we thought it would,” says Ghatnekar, president and CEO at FirstString.

“We alter how the human body responds to injury by shifting the balance from healing by scarring to healing by regeneration. The medical applications for our technology are far-ranging.”

Improving collagen matrix
The double-blind Phase I clinical study involved 49 healthy volunteers who had their scars examined. The inner biceps of each volunteer were biopsied with a 5-millimeter punch. A gel containing the alphaCT1 molecule was applied to the wound on one arm, while a control gel without any medication was applied to the other.

After the wounds had healed for 29 days, the scars were photographed and biopsied again.

Under a microscope, collagen, a protein made by fibroblast cells, formed parallel strips in the untreated scars, causing the tissue to be less flexible. Contrarily, scars treated with the molecule had a collagen matrix resembling healthy skin.

AlphaCT1 is currently being tested in phase III clinical trials in patients undergoing bilateral breast surgery.Similar outcomes were observed when related studies were replicated using guinea pig and rat models.

Examining impact on culture skin cells
The researchers also examined human skin cells cultured in a dish to observe how the drug affected cellular activity in real-time. They found that the molecule induced fibroblasts to stretch like rubber bands, then return to their original shape and shift direction.

“We call it the fibroblast dance,” says Rob Gourdie, professor of biomedical engineering and mechanics and director of the Center for Vascular and Heart Research at the Fralin Biomedical Research Institute at VTC.

“In unwounded skin, the collagen is enmeshed, allowing the tissue to move and stretch in all directions. The fibroblasts’ directional changes appear to influence how the collagen matrix forms during scarring.”

According to Gourdie, this peculiar fibroblast behavior in the treated tissue appears to benefit scar formation.

Previously, University of California San Diego researchers revealed that fibroblasts might allow for novel approaches to acne treatment in the future. The skin’s fibroblasts produce the antimicrobial peptide cathelicidin, crucial for preventing acne.

By Nicole Kerr