By Cara Murez HealthDay Reporter
Patients with an incurable, genetic liver disease have new hope after an animal study showed that a single drug could reverse its effects.
Alagille syndrome is caused by a mutation that prevents the formation and regeneration of bile ducts in the liver.
About 4,000 babies a year are born with this condition. Often, they require a liver transplant, which is not always available. Without one, about 75% will die by late adolescence.
“Alagille syndrome is widely considered an incurable disease, but we believe we’re on the way to changing that,” said study leader Duc Dong. He is an associate professor in human genetics at Sanford Burnham Prebys Medical Discovery Institute in San Diego.
“We aim to advance this drug into clinical trials, and our results demonstrate its effectiveness for the first time,” Dong said in an institute news release.
The drug is called NoRA1. It works by activating the Notch pathway, a cell-to-cell signaling system that helps orchestrate fundamental biological processes in nearly all animals and plays a role in many diseases.
The genetic mutation in Alagille syndrome causes reduced signaling, resulting in poor liver duct growth and regeneration.
In the new study, the researchers found that in animals with mutations in the same gene affected in Alagille syndrome, NoRA1 increases the cell-to-cell signaling. The study found this triggers duct cells to regenerate and repopulate in the liver, reversing damage and increasing survival.
Results of studies conducted in animals often do not pan out in humans.
“The liver is well known for its great capacity to regenerate, but this doesn’t happen in most children with Alagille syndrome because of compromised Notch signaling,” said first author Chengjian Zhao, a postdoctoral researcher in Dong’s lab. “Our research suggests that nudging the Notch pathway up with a drug could be enough to restore the liver’s normal regenerative potential.”
The researchers are testing the drug on miniature livers cultured in the lab from stem cells derived from the cells of Alagille patients.
“Instead of forcing the cells to do something unusual, we are just encouraging a natural regenerative process to occur, so I’m optimistic that this will be an effective therapeutic for Alagille syndrome,” said Dong, who is also working to form a company to bring the drug toward clinical trials. Although it will initially focus on Alagille syndrome, it may also have an impact on more common diseases, including certain cancers.
“Duc and his team continue to do thrilling research on Alagille syndrome, and these breakthroughs certainly offer hope for families living with this very complicated and complex disorder,” said Roberta Smith, president of the Alagille Syndrome Alliance.
The findings were recently published online in the Proceedings of the National Academy of Sciences.
More information
The National Organization for Rare Disorders has more on Alagille syndrome.
SOURCE: Sanford Burnham Prebys, news release, Jan. 5, 2023
14 Best and Worst Foods for Your Liver
- Reviewed By: Sabrina Felson, MD
Reviewed on 10/26/2020
Oatmeal
Food with lots of fiber can help your liver work at its best. Want one that’s a great way to start your day? Try oatmeal. Research shows it can help you shed some extra pounds and belly fat, which is a good way to keep away liver disease.
Stay Away From Fatty Foods
French fries and burgers are a poor choice to keep your liver healthy. Eat too many foods that are high in saturated fat and it can make it harder for your liver to do its job. Over time it may lead to inflammation, which in turn could cause scarring of the liver that’s known as cirrhosis. So next time you’re in the drive-thru line, think about ordering a healthier option.
Broccoli
Add lots of veggies to your diet if you want to keep your liver healthy. Broccoli can be part of this strategy. Some studies suggest this crunchy food can help protect you from nonalcoholic fatty liver disease. If steamed broccoli sounds a little too blah, shred it into a slaw and toss it with sliced almonds, dried cranberries, and a tangy vinaigrette. It’s also delicious roasted with garlic and a splash of balsamic vinegar.
Coffee
If you can’t make it through the day without it, you’ll be glad to hear that it may have some benefits for your liver. Studies show that drinking two to three cups a day can protect your liver from damage caused by too much alcohol or an unhealthy diet. Some research suggests it may lower your risk of liver cancer.
Ease Up on Sugar
Too much of the sweet stuff can take a toll on your liver. That’s because part of its job is to convert sugar into fat. If you overdo it, your liver makes too much fat, which ends up hanging around where it doesn’t belong. In the long run, you could get a condition like fatty liver disease. So do your liver a favor and make sweets an occasional treat.
Green Tea
It’s brimming with a type of antioxidant called catechins. Research suggests it may protect against some forms of cancer, including liver. You’ll get more catechins if you brew tea yourself and drink it hot. Iced tea and ready-to-drink green teas have much lower levels.
Water
One of the best things you can do for your liver is keep a healthy weight. Get in the habit of drinking water instead of sweetened drinks like sodas or sports drinks. You’d be amazed at how many calories it will save you each day.
Almonds
Nuts — especially these — are good sources of vitamin E, a nutrient that research suggests may help protect against fatty liver disease. Almonds are good for your heart, too, so grab a handful the next time you feel like snacking. Or try them in salads, where they add a nice crunch.
Spinach
Leafy greens have a powerful antioxidant called glutathione, which can help keep your liver working right. And spinach couldn’t be easier to prepare. It makes a great base for a dinner salad, and it’s also delicious sauteed with garlic and olive oil. When it’s wilted, top it with a dusting of fresh parmesan.
Blueberries
They’ve got nutrients in them called polyphenols that may help protect you against nonalcoholic fatty liver disease, which often goes hand in hand with obesity and high cholesterol. If blueberries aren’t your thing, other foods rich in polyphenols include dark chocolate, olives, and plums.
Be Moderate With Alcohol
Drinking too much can wreak havoc on your liver. Over time it can lead to cirrhosis. Even occasional binge drinking — four drinks in one sitting for women and five for men — can be harmful, too. Try to limit yourself to one drink a day if you’re a woman or two a day if you’re a man.
Herbs and Spices
Want to protect your liver and your heart at the same time? Sprinkle on some oregano, sage, or rosemary. They’re a good source of healthy polyphenols. An extra benefit: they help you cut back on salt in many recipes. Cinnamon, curry powder, and cumin are good ones to try, too.
Limit Packaged Snack Foods
Next time you feel the call of the vending machine, reach for a healthy snack instead. The problem with chips and baked goods is that they’re usually loaded with sugar, salt, and fat. Cutting back is a relatively easy diet tweak with a little planning. One good strategy: Bring a stash of healthy snacks with you to work. Try an apple with a single-serve packet of nut butter, or sugar snap peas with a mini-cup of hummus.
Medicine Net