Ohio State Medicine - Alumni Update Winter 2017

Department Collaboration Leads
to Groundbreaking Discoveries
When patients look for innovative
clinical care, they turn to the teams at
Ohio State.

One patient in particular searched across the globe for cardiac arrhythmia treatment. He was in his late thirties with recurrent ventricular fibrillation and cardiac arrest. His condition was severe and unique: neither surgical therapies nor standard pharmaceutical therapies had been effective.

In a typical patient with a potentially lethal cardiac arrhythmia, an implantable cardioverter defibrillator is a common treatment method. However for this patient, his defibrillator fired well over 100 times over just a few months, making it difficult to perform daily activities such as driving, working and spending time with his young child.

That is until he came to Ohio State for our groundbreaking treatment.

Researchers at The Ohio State University College of Medicine, Pharmacy and Engineering joined forces with clinicians in the Ohio State Heart and Vascular Center to undertake a cross-disciplinary collaboration. Peter Mohler, PhD, director of the Dorothy M. Davis Heart and Lung Research Institute (DHLRI), chair of the Department of Physiology and Cell Biology, and associate dean for Basic Research at the Ohio State College of Medicine was a member of the research team that paved the path in defining a new genetic cause and treatment for arrhythmia.

“We have an incredible team of bright,
but more importantly selfless people at
Ohio State. At every step of this story,
very busy people dropped what they
were doing to accelerate the pace of
discovery,” Dr. Mohler said.

For their first step, the team turned to innovative new genetic platforms.

Instead of examining only the handful of known cardiovascular disease genes, they utilized an innovative new research platform called “whole exome sequencing” to test the DNA sequence of all of the approximately

20,000 genes in the patient. To the team’s surprise, the group identified a completely new gene isoform and found a new potential disease variant with that novel DNA sequence.

Enlisting the help of expert cardiologists,
surgeons, physiologists, molecular
biologists and undergraduate students
was the best way to treat a disease
caused by a mutation in a gene
with unknown function. The team
determined that the new form of the
gene was responsible for regulating the
flux of potassium across the heart cell
membrane, and more importantly that
the novel human variant disrupted this
flow of potassium.

To translate the findings to patient treatment, the team utilized computational simulations to define a new therapeutic strategy based on altered cell electrical function. From this work, a new therapeutic regimen was devised based on an experimental compound used for patients with multiple sclerosis.

“While this is one great example related to heart disease, these types of stories and collaborations are now the norm at Ohio State. I am most excited that I could just as easily tell you a similar story related to translational research focused on diabetes, cancer, neuroscience, infectious disease or muscular dystrophy. While it is an exciting time to be a scientist, it is an especially exciting time to be a scientist at Ohio State,” Dr. Mohler explained.

Thus, the therapy worked to treat the arrhythmia, and the information generated from this study is now being used to design new genetic tests and potential treatments for patients with similar arrhythmias around the world.