New compounds could prevent scars even before they form

Melbourne

Scientists, including one of Indian origin, are developing new compounds that may stop scars from forming, an advance that may help people with burns and scarring disorders that impair movements and cause disfigurement.

Most people start racking up scars from an early age with scraped knees and elbows. While many of these fade over time, more severe types such as keloids and scars from burns are largely untreatable, researchers said.

These types of scars are associated with permanent functional loss and, in severe cases, carry the stigma of disfigurement.

"The treatment we're developing is focused on the major needs of patients with burns, keloids and Dupuytren contracture, a hand deformity," said Swaminathan Iyer, from the University of Western Australia.

"These patients have extensive scarring, which can impair their movements. There are no current treatments available for them, and we want to change this," Iyer said.

About 250,000 US patients undergo surgical treatment annually for keloids, which are firm, overgrown scars, and for other types of excessive scarring, Iyer said.

Researchers at The University of Western Australia, Fiona Wood Foundation and Royal Perth Hospital Burns Unit, together with Pharmaxis in Australia are studying compounds that inhibit an enzyme called lysyl oxidase, or LOX.

During scar formation, this enzyme enables the collagen involved in wound healing to crosslink. This bonding underpins the fundamental biochemical process leading to scar formation, Iyer said.

"During the scarring process, the normal architecture is never restored, leaving the new tissue functionally compromised," he said.

"So our goal is to stop the scar from the beginning by inhibiting LOX," he added.

The team tested their molecules using a "Scar-in-a-jar" model, which mimics scar formation.

This technique involved culturing human fibroblasts from scar tissues in a petri dish. The cells overproduce and secrete collagen, as they would in a real injury.

In the study, the researchers added LOX inhibitors to cultures from patients with Dupuytren's, keloids and other scar tissue, and detected changes using two-photon microscopy combined with biochemical and immunohistochemical analyses.

"The preliminary data strongly suggest that lysyl oxidase inhibition alters the collagen architecture and restores it to the normal architecture found in the skin," Iyer said.

"Once the in-vitro validation has been done, the efficacy of these compounds will be tested in pig and mouse models.

Depending on the success of the animal studies and optimal drug candidate efficacy, human trials could be undertaken in a few years," he said.

The researchers' primary objective is to help patients with severe or extensive scarring, but Iyer said that the inhibitors could potentially be used for cosmetic purposes as well. — PTI