What Causes Cachexia? Answers Could Be Found in DNA - Study

People suffering from cancer deal with all kinds of problems. Some of the more alarming signs of cancer is cachexia which is a syndrome characterized sudden loss of weight, appetite, and muscle mass. It can also manifest in patients with serious conditions such as heart disease and HIV. Finding out what causes cachexia has remained a mystery despite considerable scientific research until now. New research from the UK is raising hope that scientists are close to finding what causes cachexia. 

What is Cachexia?

Cachexia is a complex change in the body that causes weight loss even if you eat normally. Wasting syndrome or anorexia cachexia syndrome are other names for it. Cachexia is a complex problem that involves the way your body uses proteins, carbohydrates, and fat.

It is different from general weight loss. People with cachexia lose muscle and fat. Scientists think that cancer causes the immune system to release certain chemicals called cytokines into the blood. Cytokines cause inflammation and contribute to fat and muscle loss.

“In the case of patients with cancer, individuals can go from seeming quite normal to being wheelchair-bound due to muscle wasting and weight loss in only a matter of a few months,” said oncologist Professor Charlie Swanton, of the Crick Institute in London.

Cachexia results in declines in physical mobility and function. These can lead to falls, loss of independence, institutionalization, and even death.

What Causes Cachexia?

A team of scientists led by Professor Ketan Patel recently linked cachexia or wasting syndrome to DNA damage. The director of the Weatherall Institute of Molecular Medicine in Oxford connected the DNA damage to the disruption of chemical messengers sent to the brain. This causes the brain to release appetite-suppressing hormones resulting in severe weight loss.

The researchers found that naturally occurring formaldehyde can build up in a person’s bloodstream to initiate that process. When it is filtered by the kidneys, their cells suffer DNA damage. The kidneys then secrete a hormone called GDF15 to message the brain and suppress appetite.

“When you have chemotherapy, you are given a chemical substance that attacks DNA in much the same way as formaldehyde does,” said Patel. “In other words, it may be damaging DNA and triggering these signals that tell the brain to suppress appetite.”

Cockayne Syndrome

An inherited version of extreme wasting syndromes can affect children. Cockayne Syndrome  is a rare disease which causes children to suffer severe malnutrition and wasting similar to cachexia.  It is also characterized by deficient neurological development and severe sensitivity to sunlight. 

The Weatherall Institute research suggests a means of treating cachexia and Cockayne syndrome. Discovering GDF15 allows scientists to target and counter its effects. They can administer an antibody that neutralizes GDF15 to block the messages for the brain and prevent cachexia from happening.

Can it be Reversed?

“Cachexia is more than losing your appetite and weight loss, and doctors struggle to reverse this condition when it takes hold,” added Michelle Mitchell, chief executive of Cancer Research UK. 

“It is a complex problem that has an enormous impact on people with cancer, damaging their well-being and lowering their energy at a time when they need it most,” she added. “Research that can tell us more about the mechanisms behind cachexia is essential if we want to find a way to manage it.”

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