Stopping cachexia at its source could reverse wasting from cancer

People with advanced cancers often feel like their bodies are wasting away. That’s because of cachexia, a condition in which impaired metabolism leads to muscle wasting and drastic weight loss (SN: 4/15/15). A new study in mice hints at a way to reverse the condition.

Blocking the activity in the brain of an immune protein that helps regulate body weight led to the mice eating and drinking again, and even gaining muscle mass, researchers report June 1 in Nature Communications.

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There is no cure for cachexia, which occurs in an estimated 80 percent of people with advanced tumors. In some cases, the illness can become so severe that “people die not because of the tumor, but it is because of this inability to live,” says neuroscientist Bo Li of Cold Spring Harbor Laboratory in New York.

Previous research in humans suggested that elevated levels of an immune protein called interleukin-6 may contribute to cachexia. But blocking this protein in the entire body could cause severe side effects, such as irregular heartbeat. So Li and colleagues targeted the protein at the source of the problem.

In mice with cancer, the researchers injected interleukin-6 directly into the brain. The protein accumulated exclusively in a region in the brain stem called the area postrema, which is involved in triggering vomiting.

Li’s team then injected mice with an antibody that gloms onto interleukin-6, preventing the protein from docking on the surface of nerve cells in the area postrema. The researchers also used the gene-editing tool CRISPR to shut down docking stations on the nerve cells. That seemed to reverse the mice’s cachexia, the team reports.

“It’s not entirely clear if one can say, ‘I block interleukin-6 and therefore cure cachexia in humans,’” says coauthor Tobias Janowitz, a cancer scientist also at Cold Spring Harbor Laboratory. The disorder may be more complex in people than in mice, he says.

Still, Li says, “our study raises the possibility that we can actually do something” for people with cachexia. If the team can develop a treatment suitable for humans, “I think we can really help those patients and change the idea that this disease is incurable.”