TBMH graduate student awarded NIH grant to study diagnosis and treatment of genetic heart disease

People with Brugada syndrome rarely know they have it, until it makes itself dangerously apparent.

The genetically inherited heart disorder remains concealed with few apparent symptoms until it disrupts the heart’s rhythm, sometimes causing sudden cardiac death.

Grace Blair, a graduate student in Virginia Tech’s Translational Biology, Medicine, and Health Program, believes one solution to both detection and treatment could be both simple and inexpensive: sodium.

Blair, who works in the lab of Steve Poelzing at the Fralin Biomedical Research Institute at VTC, was awarded a two-year, $85,706 grant under the National Institutes of Health's Ruth L. Kirschstein Predoctoral Individual National Research Service Award program to pursue her hypothesis.

“The aim is to turn around the current thinking on the mechanism behind Brugada syndrome,” Blair said. “A lot of the current literature focuses on channels that bring potassium into heart cells. Our work focuses on the disruption of sodium channel communication. That ultimately leads to a different path of disease that hasn’t been investigated nearly as much.”

Brugada syndrome is rare, occurring in an estimated five in 10,000 people, with greater prevalence in young males, especially of Asian descent. However, it accounts for 20 percent of sudden cardiac death cases. Available diagnostic methods have limited accuracy, Blair said, and the primary treatment is installation of an internal defibrillator.

Blair aims to address both of those problems with her research.

In one part of her study, Blair will examine the loss of function of certain proteins that serve as gateways to allow sodium into heart cells. Sodium is important for maintaining electrical connections across the heart to keep it beating properly. Previous data suggest small changes to the amount of sodium around the heart can cause drastic changes in electrical conduction, Blair said.

She will use a mouse model to test whether reducing sodium in the heart causes a disruption in heart rhythms that could reveal if a patient has Brugada syndrome. If that’s the case, the method could be a new diagnostic tool for the disease. Using a mouse model, Blair will also test whether treatment with high sodium could prevent sudden cardiac death in Brugada patients.

Another of Blair’s experiments relies on a theory of heart cell communication called ephaptic coupling, in which heart cells communicate and conduct electricity based on their proximity to one another, rather than a physical connection.

When the space between the cells is increased, the communication becomes more difficult. In Blair’s hypothesis, that effect could be exacerbated in Brugada syndrome patients. She will use chemical treatments to increase that space between the cells, which should temporarily unmask the presence of Brugada Syndrome. The method could also become a new diagnostic tool.

Blair’s interest in heart disease stems from her time as a competitive cyclist. Sudden cardiac death from genetic heart problems is a regular concern among endurance athletes. Her research also furthers Poelzing’s interest in genetic diseases and deadly heart rhythm problems.

“If you could predict when someone’s going to be at highest risk for an episode that could cause sudden cardiac death, maybe it would be as simple as taking a small blood test like a diabetic does with glucose, but check their salt concentrations in their blood,” Poelzing said.

Understanding Brugada syndrome’s mechanisms could also shed light on other diseases, Poelzing said. He called the grant a great opportunity for Blair to continue important science and learn new techniques.

Blair is grateful for the award. “It’s a strong vote of confidence in me and my project, and certainly in the excellent mentorship and overall environment of the research institute, which were pivotal in our success in being awarded this grant,” Blair said.