Bike accidents, C-sections and battlefield wounds can all leave scars. But those are only the scars you can see. Any tissue can scar (not just skin), making scar tissue more than a cosmetic problem. Heart muscle, for example, can scar after a heart attack, and the lungs, kidneys, the liver, and many other tissues can be damaged by inflammation. Current options for reducing scar formation require local intervention at the scarring site – plastic surgery, for example. But what if there was a pill you could take after an injury to prevent scar tissue from forming in the first place?At Sanford-Burnham’s Center for Nanomedicine at UC Santa Barbara, Dr. Erkki Ruoslahti and his team have developed a new prototype therapy that inhibits scarring in mice. The compound contains two elements discovered by the Ruoslahti laboratory. One is a peptide that homes in on new blood vessels that form during wound healing. The other is a naturally occurring protein called decorin, which they previously showed prevents the buildup of fibrous connective tissue that causes scarring. The combination of the peptide and protein turns out to be particularly powerful.
“Nature designed scar tissue for quick closing of wounds, but scar tissue prevents the restoration of the original tissue and compromises function. New therapies are needed to promote the healing of tissue injuries without scarring,” explains Dr. Ruoslahti, senior author of the study. “Systemic treatments like the one we’ve developed may open up new treatment possibilities for preventing the long-term consequences of trauma, surgery, heart attack, stroke and many other injuries.”
The healing power of even the most promising drug is diminished if it can’t reach the right spot. The peptide portion of this new therapeutic molecule, called CAR-decorin, is made up of just nine amino acids (see Proteins 101) that selectively target new blood vessels in a healing wound, squeezes out of the bloodstream and penetrates the injured site. Once carried there by the peptide, the decorin portion blocks an inflammatory molecule called transforming growth factor-β (TGF-β). Fortuitously, as it turned out, the CAR peptide component not only carries decorin to the site of injury, but also enhances its ability to block TGF-β activity. With this CAR-decorin damper, TGF-β cannot generate the fibrotic tissue that makes up a scar.
In their study, published November 22 in the Proceedings of the National Academy of Sciences, Dr. Ruoslahti and his colleague Dr. Tero Järvinen tested CAR-decorin in mice. Beginning three days after a wound, they administered daily injections of the peptide and then measured the scar size. As they report in the paper, CAR-decorin selectively accumulated in wounds, promoted wound healing and suppressed scar formation.
“Our original results showing that decorin blocks scarring have been repeated in numerous animal studies and drugs like this are badly needed. However, decorin has never reached the clinic, most likely because decorin is difficult to manufacture in large quantities,” says Dr. Ruoslahti. “Here we demonstrate that CAR-decorin is far more active than decorin itself, which may make this compound attractive for clinical development. Beyond that, this study shows the power of the technology we have been developing for the past several years – special delivery of drugs to the site where they are needed.”
Jarvinen TAH, & Ruoslahti E (2010). Target-seeking anti-fibrotic compound enhances wound healing and suppresses scar formation in mice. Proceedings of the National Academy of Sciences.