A team of Australian researchers are working on a new treatment they claim will be able to prevent largely untreatable, potentially disfiguring scars from forming in the first place, according to a new study.

Dr. Swaminathan Iyer, a biochemist with the University of Western Australia, and his colleagues explained that they are investigating compounds that could inhibit lysyl oxidase (LOX), which is an enzyme that causes the collagen involved in wound healing to crosslink.

This, in turn, serves as the basis for the biochemical processes which can lead to the formation of severe scars in some patients – scars that the authors said are often associated with the permanent loss of function, a change in skin color and texture, and even regular discomfort and itchiness.

“The treatment we’re developing is focused on the major needs of patients with burns, keloids and Dupuytren contracture, a hand deformity,” Dr. Iyer, whose team presented their research at the 252nd American Chemical Society National Meeting & Exposition this weekend, said in a statement. “These patients have extensive scarring, which can impair their movements. There are no current treatments available for them, and we want to change this.”

Human trials could begin within the next few years

The researchers, citing statistics from the American Burn Association, said that tens of thousands of people in the US are hospitalized for burns each year. Likewise, nearly 250,000 Americans are treated each year for keloids, and an estimated 7% of have Dupuytren contracture, a condition in which connective tissue beneath the palm slowly begins to contract and become tougher.

Currently, there are no ways to treat scarring associated with any of these conditions. However, Dr. Iyer and researchers at the Fiona Wood Foundation and the burn unit at Royal Perth Hospital set out to change that by blocking LOX and preventing the processes that lead to scar formation.

“During the scarring process, the normal architecture is never restored, leaving the new tissue functionally compromised. So our goal is to stop the scar from the beginning by inhibiting LOX,” the biochemist explained. “We have been fortunate to work in collaboration with the pharmaceutical company Pharmaxis, which is designing novel and highly selective small molecules that will allow the establishment of normal tissue architecture after wound repair.”

To test the effectiveness of their compound, they created a “scar-in-a-jar” model by culturing fibroblasts from human scar tissue in a petri dish. The cells overproduced and secreted collagen just as they would with a real-world injury, but when the researchers added LOX inhibitors to the cultures, they found changes that could potentially prevent the formation of such scar tissue.

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

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Image credit: Iyer lab

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