To treat some diseases, researchers are putting immune cells on a diet

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About 12 years ago, Gary Glick and his wife noticed something wrong with their son, Jeremy. He seemed to be lagging behind his twin sister, recalls the immunologist and chemical biologist at the University of Michigan in Ann Arbor. “They were growing in unison, and he sort of stopped.” Jeremy, who was 9 or 10 at the time, also looked sickly and pale and began complaining of nagging pains in his stomach and elsewhere.

Rachel Lipson Glick, a physician, was stumped by their son’s mysterious ailment. So were other doctors. It took about 3 years to rule out myriad cancers, endocrine malfunctions, and other potential causes and to determine that Jeremy had Crohn disease, an inflammation of the digestive tract stoked by misbehaving immune cells.

The diagnosis made life harder for Jeremy, now 22 and a senior at college. To control the symptoms, he injects the antibody drug adalimumab (Humira). He will likely need it, or another immune-inhibiting treatment, for the rest of his life.

By coincidence, one of those alternatives might stem from his father’s work. Gary Glick, like an increasing number of other researchers, is convinced that the immune cells driving conditions such as Crohn disease share a feature that could be their undoing: their metabolism. He has spent the past 2 decades searching for drugs that target metabolic adaptations of immune cells. Clinical trials by Lycera, a company Glick founded, are now assessing the first of those drugs for psoriasis and ulcerative colitis, an intestinal illness related to Crohn disease.

Drug companies are working to develop other candidates. Researchers are also looking to deploy existing drugs that tamper with metabolism, such as the diabetes treatments metformin and 2-deoxyglucose (2DG). “It’s a very exciting time,” says immunologist Jonathan Powell of Johns Hopkins University’s School of Medicine in Baltimore, Maryland. “Potentially, all immunologic diseases are targets for metabolic therapy.”

Cancer researchers have also tried to disrupt cell metabolism, even testing some of the same drugs immunologists are investigating. But many scientists are convinced the strategy will work better for immune diseases than for tumors because drugs to treat those illnesses need only to suppress a relatively small number of overexuberant cells, not eliminate them. And whereas existing drugs that restrain immune cells, such as adalimumab, can compromise our defenses against pathogens, Glick and other scientists think that drawback won’t affect their strategy. Focusing on the metabolism of overactive immune cells, he says, offers “a way to directly target these cells while sparing immune function.”

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