Scars, Keloids & Dupuytren Contracture can be Prevented by Enzyme LOX

Scientists are developing new compounds to stop scars from forming in the first place and avoid excess scar formation such as keloids.

Highlights

Scars occur when tissues have been damaged or repaired.
Scars from 3rd degree burns, keloids, Dupuytren contracture are untreatable
LOX enzyme shows promising results in the scarring process

Scars are common. Many of the scars fade away or disappear over a period of time. Scars can occur inside and outside the body. More severe types such as keloids or scars from deep burns are untreatable. These types of scars are associated with functional loss (permanent) and in severe cases, carry the stigma of disfigurement.

To help prevent severe scars Iyer and colleagues at The University of Western Australia, Fiona Wood Foundation and Royal Perth Hospital Burns Unit, together with Pharmaxis Ltd., (all in Australia) are in the process of developing new compounds which could stop the scars forming in the first place.

Burns - First Aid and Emergency Treatment Guide
A quick and simple first aid guide on how to administer treatment for first degree and second degree minor burns. Third Degree Burns usually require hospitalization.

‘Lysyl oxidase (LOX) inhibitors help patients with severe or extensive scarring after surgery, injury or burns.’

"The treatment we're developing is focused on the major needs of patients with burns, keloids and Dupuytren contracture, a hand deformity," says Swaminathan Iyer, Ph.D. "These patients have extensive scarring, which can impair their movements. There are no current treatments available for them, and we want to change this." A survey by RTI International found that an estimated 7 percent of Americans have Dupuytren contracture, a hand condition.

Types of Scars

Flat, pale scars are the most common type of scars
Hypertrophic scars are red, raised scars that form along a wound
Keloid scars are caused by an excess of scar tissue at the site of the wound, about 250,000 US patients undergo surgical treatment for keloids.
Pitted scars have sunken appearance
Contracture scars are caused by skin shrinking and tightening due to burns

How Do Scars Form?

When the skin is damaged or if it is opened in surgery and there is a break.
Collagen protein is produced as a part of the healing process.
Collagen buildups when the tissue has been damaged and helps heal the wound.
During the course of time (three months or longer) due to the formation of new collagen, the blood supply to the area increases, this causes the scar to become raised, lumpy and red.
Some collagen breaks down at the site of the wound, resulting in reduced blood supply thereby the scar becomes smoother, softer and paler.

LOX Enzyme

Lysyl oxidase (LOX) is a protein in humans encoded by the LOX gene. LOX is also known as protein lysine 6 oxidase. During the formation of scars, LOX enzyme enables the protein collagen (involved in wound healing process) to crosslink. This crosslinking process underpins the basic biochemical process that leads to scar formation.

Puncture Wounds - First Aid and Emergency Treatment Guide
A quick and simple First Aid guide on how to administer treatment for Puncture Wounds.

"During the scarring process, the normal architecture is never restored, leaving the new tissue functionally compromised," explains Iyer. "So our goal is to stop the scar from the beginning by inhibiting LOX. 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."

Scar-in-a-Jar Model:

Skin cells walk to wounds to repair it
How the skin cells will alter the proteins holding them in place and move to repair a wound has been observed by Washington State University researchers.

"Scar-in-a-jar" model which mimics the scar formation process was used by the research team. The experimental procedure was as follows -

Human fibroblasts were cultured from scar tissues in a petri-dish.
The cultured cells overproduced and secreted collagen as in a real injury.
LOX inhibitors from patients with Dupuytren's, keloids and other scar tissue were added to the cultures.
LOX inhibitors were found to alter the architecture of collagen and restore it to a normal architecture found in the skin.

"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.”, Iyer says.

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

The research work is to be presented at the 252nd National Meeting & Exposition of the American Chemical Society (ACS).

Ways to Reduce the Appearance of Scars

Avoid scratching the wound
Cover the wounds with a waterproof ointment
Use silicone gels to reduce redness and promote healing

References

Introduction to Scars - (http://www.nhs.uk/conditions/Scars/Pages/Introduction.aspx)

Source-Medindia