Researchers report in the journal Cell Reports a targeted molecular¹ therapy that dramatically reduces the initial development of Non Alcoholic² Fatty Liver Disease (NAFLD) in laboratory mouse models of the disease. The study, published online June 30, found increased levels of an enzyme³ called cdk4 in patients with NAFLD and in mouse models. Researchers at Cincinnati Children's Hospital Medical Center report that when they used two drugs that inhibit⁴ cdk4 in mouse models of NAFLD (flavopiridol, PD-0332991), this significantly reduced development of hepatic steatosis - the first stage of the disease.

 

"This is the first study to show that cdk4 triggers development of NAFLD and that inhibiting⁵ this enzyme can both prevent and reverse the first step of the disease," said Nikolai Timchenko, PhD, senior author and head of the Liver Tumor⁶ Biology Program at Cincinnati Children's. "Both of the cdk4 inhibitors we tested are approved by the FDA and in clinical trials for liver cancer, so it should be possible to initiate⁷ clinical trials for NAFLD with these drugs soon."

 

NAFLD is an abnormal buildup of extra fat in liver cells that is not caused by alcohol. The disease - which affects up to 25 percent of the U.S. population - usually develops in people who are overweight, obese⁸ or have diabetes⁹ and high cholesterol¹⁰. The first stage of the disease, hepatic steatosis, can progress to a condition called NASH (non-alcoholic steatohepatitis) and ultimately cirrhosis or liver cancer. 

 

Timchenko said new therapies for NAFLD are needed because, short of weight loss and lifestyle changes, there currently are no safe or effective treatments. There are new treatments being tested in clinical trials with promising¹¹ results, but these studies have revealed evidence of serious side effects.

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