When Spencer Gibson arrived at the University of Alberta four years ago to assume his new role as the Dianne and Irving Kipnes Endowed Chair in Lymphatic Disorders in the Faculty of Medicine & Dentistry, he knew the task ahead of him was a monumental one.
"There was nobody doing this work in Canada," recalls the professor of oncology and member of the Cancer Research Institute of Northern Alberta. Though there were basic researchers focused on lymphatics, he was the only one who would be working in the more narrowly focused area of lymphedema.
"It's an underappreciated, understudied area, and I started this program from scratch," he says.
There are two types of lymphedema: primary, in which a person is born with a genetic mutation that results in the malformation of their lymphatic systems; and secondary, in which damage is inflicted upon a healthy lymphatic system due to external factors such as cancer treatment, infection or injury. Both are characterized by painful swelling of the extremities due to fluid buildup. And both are currently treated by compression garments or manual lymphatic drainage, neither of which has lasting effects.
"Once you stop, it comes right back," says Gibson.
Dianne Kipnes, a longtime donor to the University of Alberta along with her husband Irving, was one of the million people in Canada living with secondary lymphedema until her passing last December. It is thanks in large part to the Kipnes family's funding of his chair that Gibson and his team have been able to study the condition's potential causes and treatment.
"Why do some people who have damage to the lymphatic system get lymphedema while others are perfectly fine?" That's the question Gibson set out to answer in his latest study, published in EMBO Molecular Medicine. Operating on the theory that something in a patient's microenvironment likely makes them more susceptible to lymphatic blockage, the team hoped to gain an understanding of what that might be with the ultimate goal being treatment and, hopefully, prevention.
To find answers to his question, Gibson spent more than three years gathering a biobank of 70 patient blood samples to test and, because obesity and being overweight are known risk factors for lymphedema, began by looking at lipids. Using the Faculty of Medicine & Dentistry's Flow Cytometry Facility and Cell Imaging Facility, the team soon learned there was a lower level of good fats than bad in the samples from individuals with lymphedema. When tested in an animal model, a high-fat diet either brought on or worsened lymphedema, while switching back to healthy food reversed the effects.
"This clearly shows us diet is contributing to the progression of lymphedema," says Gibson. But how to explain the fact that the vast majority of us are eating the same western diet high in saturated fats, but not all of us are getting lymphedema?
Previous cancer research had established that a "chaperone" that carries fatty acids into the cells — called fatty acid binding protein 4 (FABP4) — is found in amounts 2.8 times higher in lymphedema patients than in those without. The team found that inhibiting FABP4 in an animal model — using a chemical inhibitor that was already being used in clinical trials for other reasons — resulted in a 50 per cent reduction in lymphedema.
Gibson now hopes to connect his two discoveries and translate them into meaningful treatments that will improve the lives of those with lymphedema, tackling the problem from multiple angles. His short-term goal is to find out the effects of a low-saturated-fat diet — which should mean the FABP4 can focus its work on binding to good fats instead. He's also looking to identify treatments that target other sources of stress to the microenvironment, such as cancer treatment, hypoxia and oxidative stress.
"The environment of collaboration at the U of A is very healthy," he says, citing the newly launched Dianne and Irving Kipnes Health Research Institute and his partnerships with others across the College of Health Sciences who bring a broad range of expertise to work toward solutions such as diet, supplements and even repurposing existing FDA-approved drugs. These include Catherine Field, professor emeritus and expert in lipid biology, and Carla Prado, Tier 1 Canada Research Chair in Integrative Nutrition, Body Composition, and Energy Metabolism, both from the Faculty of Agricultural, Life & Environmental Sciences; and Margaret McNeely, professor in the Faculty of Rehabilitation Medicine and adjunct in the Department of Oncology.
These days, Gibson is tremendously encouraged about the future of this research. He used to joke, "I'm the number one molecular biologist working in lymphedema in the country. And you know why? It's because I'm the only one!" But an ever-growing group of trainees shows him that very short list is increasing exponentially. He also sees word of mouth from patients influencing his work, and believes that too will grow the more studies come online.
"Patients who participate in studies share their experiences and this creates hope for others. In this way, we create a positive feedback loop. This is a two-way street, with patients contributing to the research and research contributing to the patients."
