Steven Poelzing

By Jim Stroup/Virginia Tech

Steven Poelzing

Study proves pivotal for patient with rare disease

For scientists conducting basic biological research, discoveries often take years before they’re translated into effects on individual patients. Even if they lead to clinical trials, the impact on human health is not a guarantee. Imagine the delight, then, when a scientist sees a research paper have a dramatic effect on a patient less than a year after publication.

This is what happened to Steven Poelzing, an associate professor at the Virginia Tech Carilion Research Institute, who studies the electrical wiring and signals that keep a heart pumping. Included in his studies is research on a rare genetic disease called Andersen-Tawil syndrome, which shorts and crosses some of those cardiac wires causing arrhythmias. Just a year ago, Poelzing published a paper on a potential treatment for the disease that proved to be just what two doctors didn’t know they had ordered.

Andersen-Tawil syndrome is a genetic disease that causes arrhythmias in one of the heart’s ventricles. When an increasing number of heartbeats become abnormal, the strain it places on the body’s most important muscle can lead to further heart disease and an early death. However, because the condition is so rare – only about a hundred cases have been reported worldwide – pharmaceutical companies have not shown interest in developing new treatments.

Luckily, many people affected by Andersen-Tawil syndrome respond well to drugs that were developed to treat other heart conditions. One example is verapamil, which is also often prescribed to treat hypertension. But not everyone responds well to common treatments.

Earlier this summer, an adolescent undergoing treatment for Andersen-Tawil syndrome at the Children’s Hospital of Philadelphia suffered from an ever-increasing number of abnormal heartbeats despite the doctors’ best efforts. Once the disease progressed to the point at which more than half the patient’s heartbeats were arrhythmic, the doctors turned to recent studies in basic biochemistry for hope.

What they found was Poelzing’s study.

“These doctors wanted to know, based on my paper, whether I’d recommend a specific therapy,” recalled Poelzing. “My first reaction was that you should ask another doctor; I’m not qualified to affect patients’ lives. But I responded by letting them know what I thought would happen.”

Many traditional arrhythmia therapies work by controlling the flow of calcium ions between heart cells. Poelzing reasoned that because previous studies have shown that increased arrhythmias come from regions with high sodium-calcium exchange rates, controlling the amount of sodium entering heart cells might also have a positive effect. In a paper published in 2013, Poelzing showed that blocking certain sodium channels could indeed work to better regulate an abnormal heartbeat. But there were two important caveats to using the results as a basis for treatment in humans.

“The original study was conducted in guinea pigs,” said Poelzing. “It was also a drug-induced model of the disease, whereas the normal manifestation in human beings is because of a genetic mutation. I think my research was a last-ditch effort.”

The Philadelphia doctors decided to give the idea a shot and prescribed their patient a low dose of both verapamil, a calcium channel blocker, and flecainide, a sodium channel blocker.

In less than two weeks, the patient’s rate of arrhythmic heartbeats dropped from 56 percent to below 5 percent.

And it has stayed there for months.

“I think the physicians deserve the credit for doing their homework and figuring this out,” says Poelzing, who has had no contact with the patient and does not even know his or her identity. “And while there is no typical ‘feel-good’ moment where I get to meet the patient, my feel-good moment comes from realizing my research has affected someone so positively. But it’s important to remember that this is only a single person. The treatment would have to go to a clinical trial to show efficacy, and I don’t know that there are enough people that have the disease to conduct one.”

Moving forward, Poelzing and his team will examine in greater depth whether these drugs and other drug combinations are important for this disease as well as diseases with similar arrhythmia mechanisms.

“We study Andersen-Tawil syndrome – despite its rarity – first because it matters to those few people who have it,” said Poelzing. “And second, the symptoms resemble those that occur when people develop cardiac disease. It’s interesting because you can see what happens if you change just one parameter in the body – like losing a cardiac potassium channel – versus going into something as complicated as heart disease, where many variables change simultaneously.”

Written by Ken Kingery