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New Drug to Fight Liver Fibrosis, the Wound That Never Heals

by Dr. Trupti Shirole on  December 13, 2015 at 8:32 AM Research News   - G J E 4
Liver fibrosis refers to a condition involving chronic damage to the liver which eventually creates a wound that never heals. This condition gradually replaces normal liver cells - which detoxify the food and liquid we consume - with more and more scar tissue until the organ no longer works.
 New Drug to Fight Liver Fibrosis, the Wound That Never Heals
New Drug to Fight Liver Fibrosis, the Wound That Never Heals
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Scientists at the Salk Institute have identified a drug that halts this unchecked accumulation of scar tissue in the liver. The small molecule, called JQ1, prevented as well as reversed fibrosis in animals and could help the millions of people worldwide affected by liver fibrosis and cirrhosis, caused by alcoholism and diseases like hepatitis. These results were published in PNAS.

‘Salk Institute researchers have identified a drug that halts the unchecked accumulation of scar tissue in the liver. This small molecule, called JQ1, prevented as well as reversed fibrosis in animals.’
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Ronald Evans, professor and director of Salk's Gene Expression Laboratory and a Howard Hughes Medical Institute investigator, said, "After too much damage in the liver, the scar tissue itself causes more scar tissue. We can actually reverse liver fibrosis in animals and are now exploring potential therapeutic applications for humans."

When the liver is damaged, small collections of hepatic stellate cells that specialize in storing vitamin A are called upon to tend to the wound. These activated stellate cells shed their vitamin A, travel to the site of injury and create thick, fibrous scar tissue to wall off and repair the damage. However, with prolonged organ stress, healthy liver cells become replaced by scar tissue, eventually leading to organ failure.

Michael Downes, a Salk senior scientist and author of the paper, said, "Traditional therapies targeting inflammation don't work because these cells have multiple ways to bypass the drug. In contrast, our strategy was to stop the fibrotic response at the genome level where these pathways converge."

The search for the critical genome pathway struck gold, uncovering a regulatory protein, called BRD4, that is a master regulator of liver fibrosis.

With this new knowledge in hand, the Salk team found JQ1 successfully inhibited BRD4 and halted the transformation of hepatic stellate cells into fiber-producing cells. This is good news, as JQ1 is a prototype of a new class of drugs currently being tested in human clinical trials for various cancers.

Ruth Yu, a Salk staff researcher and one of the authors of the paper, said, "JQ1 doesn't just protect against the wound response, but also reverses the fibrotic response in mice."

Evans, who also holds the March of Dimes Chair in Molecular and Developmental Biology, said, "Our results indicate that BRD4 is a driver of chronic fibrosis and a promising therapeutic target for treating liver disease. We think this discovery may also treat fibrosis in other organs, like the lung, pancreas and kidney."

Source: Eurekalert
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