Your dog is looking a little thin. Is that simply a sign that he has been getting a lot of exercise and needs a bit more food in his bowl, or is he losing muscle mass because of an underlying disease?
Cachexia, a metabolic condition that can be a side effect of heart disease, cancer, or a number of other diseases, leads to muscle loss and weight loss that can’t be reversed by eating more. Veterinarians frequently discover it by feel as there is no standardized test for detecting it. By the time it is discovered, there are usually few options for slowing or reversing the process and the underlying disease causing it.
Researchers at Cummings School of Veterinary Medicine are now working with engineers at the Massachusetts Institute of Technology (MIT) to determine whether a blood test, ultrasound, or a combination of both can be developed to detect cachexia sooner, more consistently, and to grade how advanced the condition is.
Efforts to develop a blood test focus on extracellular vesicle biomarkers (EVs), a relatively new field of scientific discovery. EVs are packets of particles sent out by cells which contain genetic material such as mRNA, microRNA, as well as growth factors, inflammatory cytokines and other substances, explains Vicky Yang, D.V.M., Ph.D., associate professor of clinical sciences at Cummings School and a member of the research project team.
Not unlike an SOS distress signal, these packets can trigger other cells in the body into action. Sometimes what they trigger has positive effects. Other times the results are negative, Yang says.
“Are the EVs blocking the expression of good genes that could help, in which case we should try to block the EVs, or are they promoting repair, in which case we should find ways to encourage that process further?” says Yang. “By developing a way to detect the presence of EVs that signal muscle loss and determining what the EVs are triggering, we can potentially provide a way to not only diagnose cachexia, but point to ways to intervene in the process.”
The Tufts researchers are collecting donated muscle from deceased normal dogs, as well as deceased dogs who had cachexia to extract EVs from each and compare them for differences. “We have a great program at Tufts that enables pet owners to donate tissue from their pet for research when they die, which helps us in efforts like this,” Yang says.
If the scientists pinpoint differences in EVs from donated tissues obtained from dogs with and without cachexia, they will have a better idea as to what they should be looking for in blood samples collected prospectively from dogs presenting to their veterinarians to screen for cachexia.
Yang says if successful, results from this study in dogs could ultimately lead to similar approaches to develop a biomarker test in humans, who also develop cachexia in response to underlying heart disease, cancer, and other diseases.
Yang is working on this project with collaborators Lisa Freeman, D.V.M, Ph.D., DACVIM, professor in the Department of Clinical Sciences at Cummings School, and MIT principal research scientist Brian Anthony, who is exploring whether an ultrasound test can be devised to detect and grade cachexia.
This research is part of a larger project led by Cheryl London, D.V.M., Ph.D., DACVIM, associate dean for research and graduate education at Cummings School. London is a veterinary oncologist/immunologist and the principal investigator on an RC2: High Impact, Interdisciplinary Science grant, which is associated with a parent UM1 Clinical and Translational Science Award to Tufts from the National Institutes of Health. Yang, Freeman, and veterinary oncologist Heather Gardner, D.V.M., Ph.D. DACVIM are co-investigators. Their goal is to leverage clinical trials in pet dogs to optimize early detection of both cancer and heart disease, and then translate these advances into human health.
