Discovery May Improve Treatment for Cancer-Related Condition

A protein-neutralizing antibody may curb or prevent symptoms of cachexia.

Unfortunately, the American Cancer Society predicts that more than 1.6 million Americans will be diagnosed with cancer this year, with nearly 38,000 new cases in Massachusetts alone. Roughly half of all cancer patients will develop cachexia, a debilitating condition characterized by loss of weight and muscle mass which can decrease chances of survival.

Until now, successful treatment of the condition has been limited, but new research published in the journal, Nature, by scientists at Harvard Medical School (HMS) and Dana-Farber Cancer Institute, may change that. In an experiment featuring mice with lung tumors, researchers discovered that administering a polyclonal antibody improved or prevented the symptoms of cachexia.

According to a Harvard report, the antibody “blocked the effects” of a tumor-secreted protein known as PTHrP:

This tumor-derived protein, [researchers] found, stimulated ‘beige’ fat cells—brown fat cells mixed with stored white fat in the body. The stimulation caused the white fat to ‘brown’—that is, to generate heat and cause weight loss even when the animals were at rest.

The researchers carried out two experiments using mice that developed lung tumors and cachexia. In one, they administered a polyclonal antibody that specifically neutralizes PTHrP and found that it prevented the wasting almost completely, while untreated animals became mildly cachexic.

In a second experiment, the antibody treatment prevented the loss of muscle mass and improved muscle function, while control animals developed severe muscle wasting.

Bruce Spiegelman, the study’s lead researcher and an HMS professor, said in the report that his team was surprised by the treatment’s positive effects on health and loss of muscle mass. According to the report, “the research suggests that PTHrP alone doesn’t directly cause muscle wasting, yet blocking the protein’s activity prevents it.”

Despite the success of the experiment, Spiegelman said more work is needed before the antibody treatment is used with human patients.

“Clinicians would probably first want to find out if the protein is elevated in certain cancers, and determine which patients would be good candidates for a clinical trial,” Spiegelman said in the report.