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Genetics - Research news
Genetic tinkering turns back cirrhosis
Last updated: Monday, January 17, 2005
When people think of scars, the first things that usually come to mind are the marks of old injuries on the skin. But traumatised internal organs can scar too, wreaking havoc on the inner workings of the body.

 
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For several years, scientists have been trying to find ways to stop and even reverse excessive scarring. Now, American and British researchers say they are close to figuring out how to do that for patients with cirrhosis, an often-fatal liver disease characterised by scarring. If successful, the treatment may help patients with severe burns, cystic fibrosis and other ailments.

The key is reprogramming a protein whose job is to make scarring happen. "It's a completely different approach, not just another antibiotic," says Dr Mario Chojkier, co-author of a new study and professor of medicine at the University of California.

While cirrhosis is closely connected to alcoholism - an estimated half of men who drink more than eight drinks a day will develop the ailment - it's also caused by hepatitis and other diseases.

As liver disease progresses, toxins poison the organ and cause scar tissue to build up, blocking blood vessels that travel through it. "It's like clogging a pipe. It makes the blood flow go backwards, which will have major consequences. Things that are good or bad for the body can't be handled accordingly by the liver because the blood can't reach it," Chojkier says.

Other problems can develop, like yellowish skin (known as jaundice), bleeding and liver failure.

While doctors can try to stop the causes of cirrhosis, they haven't been able to turn back time on scarring. "We have to accept that we cannot treat everybody. That's why we need alternatives," says Dr Adrian Di Bisceglie, medical director of the American Liver Foundation.

That's where the US and UK researchers come in. Their findings appear in the October 26 issue of the medical journal Molecular Cell.

By tinkering with the genetics of a protein so that it no longer has an amino acid that starts an excessive scarring process, they have changed the way scars develop in mice with liver disease.

Existing scar tissue may even evaporate, a process called "melting" by some researchers. "It could get back to normal little by little," Chojkier says.

Experiments on humans may come in the next several years. With luck, the new treatment "could be utilised for the prevention of fibrosis [scarring] in other organs, like the lungs and kidney and skin and the brain. We think if it works in one organ, it has a very good chance of working in another," Chojkier says.

Liver disease experts say the new research is intriguing, but they caution that successful research in mice doesn't always translate to human treatments.

The findings are part of a "growing body of information and excitement" in the medical community about the prospects of stopping and reversing scarring, says Dr Scott Friedman, professor of medicine at Mt Sinai School of Medicine.

Even without the new research, doctors can do much more for liver disease patients than in the recent past, Di Bisceglie says. "If you go back 10 or 15 years ago, we had very few treatments. In the last 10 years, we've seen a lot of developments like liver transplants, which we do 4 000 to 5 000 times a year in this country. There are treatments that are increasingly effective."


 
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