Pediatric Liver News
February 14, 2013

Researchers have long known that the sequences of components that make up genes— both ours and germs’—have a powerful influence on diseases and infections. Outcomes of conditions ranging from cancer to the common cold depend heavily on exactly how the four nucleotides that make up DNA line up. But that’s not the end of the genetic story. It turns out that genes, in turn, have their own influences. Over the past several decades, scientists have come to a growing awareness that a host of pressures, most notably chemical “tags” that clip onto DNA like charms on a bracelet, can sway the course of illnesses just as heavily as DNA itself.

According to pediatric hepatologist Douglas Mogul, the study of these gene influencers (known as epigenetics, which means “above the genome”) could also sway the search for new treatments, especially in his own field of hepatitis B. Because current drugs to treat this disease are only effective for 25 percent of children who take them, he explains, hepatitis B is ripe for more effective pharmaceuticals. Drugs that affect the epigenetics of this disease could hold unprecedented promise in treating it.

The more researchers learn about the epigenetics of hepatitis B, Mogul adds, the closer these new generation drugs come to fruition. Recently, Mogul’s colleague, Hopkins researcher Michael Torbenson, discovered that when the virus that causes this disease carries certain chemical tags—methyl groups clinging to distinct segments of its DNA—it seems to be less infectious for liver cells living in petri dishes.

This knowledge could be extremely helpful for developing new drugs, Mogul says. Treatments that add methyl groups to viral DNA might stem the tide of rising infection, but only if this rule also applies to real patients and not just cultured cells.

To see if that’s the case, Mogul and his colleagues are currently working on two different multicenter studies on hepatitis B patients. In one of these studies, the researchers are taking blood samples from patients with a range of different disease states, some with mild infection and others with more severe hepatitis B. By looking at the methyl groups on these patients’ viral DNA, the researchers are checking to see whether those patients whose viruses carry more methyl tags have lower levels of infection, confirming the cell culture work.

In another study, Mogul and his coworkers are examining the diets of patients with differing degrees of infection. Since some foods contribute methyl groups, they might theoretically add them to the hepatitis B virus, giving researchers another avenue to treat this disease.

“By looking at hepatitis B in this very different way,” Mogul says, “we could open the door to a whole new set of treatments we couldn’t have C found through any other pathway.”