U of A researchers aim to prevent muscle wasting that causes many cancer deaths

Researchers at the University of Alberta are looking for ways to prevent or slow cachexia, a muscle-wasting syndrome thought to cause up to a third of the 80,000 deaths related to cancer every year in Canada.

By understanding the role of activin A, a growth factor that contributes to muscle wasting, the team hopes their lab research will eventually help treat patients, improve their quality of life and reduce mortality, said project lead Xavier Clemente-Casares, assistant professor in the Department of Medical Microbiology & Immunology.

Activin A is a key developmental factor for the heart during the embryonic stage, but after birth it plays other roles that aren’t fully understood, Clemente-Casares explained. Previous research has established that it contributes to cardiac and other muscle wasting, especially in patients with advanced cancer. Chemotherapy is also known to contribute to muscle wasting.

In the first stage of the project, the collaborators will design and develop a cell-based sensor to detect activin A signalling pathways and see whether they are turned on in the cell lines. In the second stage, the researchers will use the Faculty of Medicine & Dentistry’s library of thousands of drug compounds and test whether any are effective in stopping the pathway-signalling process.

“The idea is that muscle wasting stems from this unwanted activation of the pathway,” explained collaborator Amit Bhavsar, an assistant professor in the Department of Medical Microbiology & Immunology with expertise in drug validation. “We want to find a way to modulate this pathway, to control how active it is, so we can prevent it from rampantly turning on and leading to this wasting. It would certainly improve the lives of patients if there was a way to do this.”

Despite delays caused by the COVID-19 pandemic, Clemente-Casares hopes the first stage of the project can begin by summer, with the drug-testing stage to follow later this year or next year. He is grateful for a seed grant from the Precision Health signature area because most big funding agencies don’t finance this kind of first-step basic research.

“I think it’s important as a basic researcher to start moving to how to apply our basic knowledge to something that, at some point, can help patients,” said Clemente-Casares, who along with Bhavsar is a member of the Cancer Research Institute of Northern Alberta and the Women and Children’s Health Research Institute.

Further research and pre-clinical trials will require larger funding and the involvement of a more multi-disciplinary team including U of A chemists, pharmaceutical scientists and others.

While the research is in very early stages, the team is optimistic it will eventually benefit cancer patients.

“If we find something and publish it, and someone else sees it and goes, ‘We can contribute to that,’” said Bhavsar, “as long as it helps patients, that’s the important part.”

Source: University of Alberta