London: Scientists have created a molecule that could fully reverse the devastating muscle loss that often accompanies advanced cancer in mice and thereby increased the lifespan of animals with the disease.
The molecule blocks the activity of a key muscle-limiting protein called myostatin by acting as a decoy.
Instead of myostatin binding to its normal receptor and triggering muscle wastage, it is ``mopped up`` by binding to the decoy molecule instead.
Muscle wasting — called cachexia — is thought to account for about 30 percent of deaths in patients with cancer, but how exactly cachexia is spurred by cancer — or indeed exactly how it leads to a patient’s decline — isn’t known.
It is thought that several molecular pathways work in tandem, "activating an axis of evil to control muscle mass in a negative way", said H. Q. Han, lead author of the study and scientific director of the metabolic disorders division at Amgen, a biotechnology company in Thousand Oaks, California.
The researchers wanted to find the dominant pathway responsible for cancer cachexia, and then design a way to block it in order to treat patients.
Several studies have shown that blocking the myostatin pathway can promote muscle growth, said Han, and some have shown that a molecule closely related to myostatin, called activin A, becomes more abundant in patients with some cancers.
"We examined a large random collection of cancer cell lines in vitro, and found that one-third of them secreted large amounts of activin A. This led us to believe that activin A must have some systemic function when overproduced in a cancer setting," Nature quoted Han as saying.
The researchers created a soluble version of the activin A receptor — which is thought to affect both myostatin and activin A signalling — by fusing a piece of human activin receptor to an antibody.
This decoy mopped up the ligands that usually bind to the real receptor, thus blocking receptor activation.
“There’s really an overwhelming amount of data now showing the benefits of targeting this pathway,” said Han.
A single injection of the soluble receptor into normal mice boosted their muscle mass by 25 percent or more in a week or two.
When it was given to mice implanted with colon cancer cells, their muscle mass returned to normal, even though their tumours continued to grow.
Strikingly, all of the animals that did not receive the soluble receptor were dead 40 days after cancer cells were implanted, but more than half of the treated animals survived to this point.
The study will be published in the journal Cell1.