Drug trial aims to fight heart disease by thinning the field

Study targets individuals with a genetic mutation linked to thickened heart muscle
May 19th, 2017

 

Tarryn Ford, left, with her mother, Leslie, and dogs London and Ainsley. Tarryn is in a clinical trial at UCHealth University of Colorado Hospital of a drug designed to treat hypertrophic cardiomyopathy in individuals with a genetic mutation linked to the disease.
Tarryn Ford, left, with her mother, Leslie, and dogs London and Ainsley. Tarryn is in a clinical trial at UCHealth University of Colorado Hospital of a drug designed to treat hypertrophic cardiomyopathy in individuals with a genetic mutation linked to the disease.

At first glance, Tarryn Ford’s life offers few surprises.

Ford, 30, teaches math to kids from kindergarten through sixth grade in Manhattan, Kansas. When she’s away from that time-consuming job, she walks and plays with her two golden retrievers and hangs out with friends and family. She makes occasional trips to Colorado to visit an aunt in Highlands Ranch. Asked to describe how she feels, Ford says, “Pretty normal.”

So why is Tarryn Ford in a clinical trial at UCHealth University of Colorado Hospital?

It turns out that in at least one way, Ford’s life is very different from most others: She has one of a number of genetic mutations linked to a disease called hypertrophic cardiomyopathy (HCM) that causes thickening of the heart muscle. Over time, that abnormality can weaken blood flow and lead to a host of problems, including chest pain, fatigue, shortness of breath, hypertension, arrhythmia and even sudden death from cardiac arrest.

For now, Ford says she feels no symptoms. But she knows she is at greater risk for HCM than most. Her grandmother, who passed away several years ago, was diagnosed in her late 70s with HCM through genetic testing. Ford’s father also carries the genetic mutation. With that in mind, Tarryn initiated testing at UCH a little more than two years ago. It revealed that she too possesses the trait and is therefore at increased risk for developing HCM.

Joining a select group

After additional testing, including blood work, EKGs, MRIs, and physicals, Ford qualified for a clinical trial of valsartan, a drug already used to treat patients with high blood pressure and heart failure. The study focuses on patients like Ford, who have an HCM-linked mutation, but are young and relatively healthy. Patients receive either valsartan or a placebo. Researchers will study various measures of the subjects’ cardiac health – blood pressure, blood flow capacity, and the structure of the heart muscle, for example – and progression of the disease to discover if valsartan is more effective in treating this group of patients than a placebo.

The trial, led by Brigham and Women’s Hospital in Boston and funded by the National Heart Lung and Blood Institute of the National Institutes of Health, is an example of so-called personalized or precision medicine. Rather than administering valsartan or another drug broadly to all people with HCM, researchers are targeting people like Tarryn Ford who have HCM due to a specific genetic profile.

Changing the conversation

“It’s emblematic of where we are headed with clinical trials,” said Matthew Taylor, MD, PhD, director of Adult Clinical Genetics at UCH, who supervises Ford’s care in the study. Taylor is also an associate director of the Colorado Center for Personalized Medicine, which includes a DNA Biorepository for genetic testing and research on the University of Colorado Anschutz Medical Campus.

Taylor noted that favorable response rates to medications given patients for many diseases are often only 20 to 50 percent.

Matthew Taylor at work in the Adult Genetics Clinic at UCHealth UCH, which he directs. Taylor, who supervises the care of Tarryn Ford, says trials like the one she is enrolled in are slowly changing the way clinicians practice medicine
Matthew Taylor at work in the Adult Genetics Clinic at UCHealth UCH, which he directs. Taylor, who supervises the care of Tarryn Ford, says trials like the one she is enrolled in are slowly changing the way clinicians practice medicine

“The remainder don’t respond, but we can’t pick them out beforehand,” he said.

By contrast, the valsartan trial and many others are using genetic testing to try to improve the odds of success, Taylor said. “We’re finding subsets of patients with genetic mutations who are more apt to respond” to targeted therapies, he noted. “There are many different medications, and the idea is to tailor and customize treatment for patients. It’s a shift in the way we practice medicine.”

The valsartan trial also points toward taking a more proactive approach to treatment, Taylor noted. In a patient like Tarryn Ford, who thus far shows no symptoms of HCM, for example, the drug might slow down or even halt its progression. If so, many patients would be spared seeking treatment only after the disease causes damage to the heart that interferes with their everyday lives and heightens their vulnerability to ongoing health problems.

“The trial is not completely about prevention, but that is one of the goals,” Taylor said.

Widening understanding

More broadly, Taylor notes that genetically driven studies that focus on a specific disease open the door to discoveries that help people with other conditions. “The more we understand the genetic and biological basis of disease, the better we will able to select the right drug for the right patient,” he said.

While he is optimistic about the possibilities of these new approaches, Taylor is careful to note the limitations. Age, gender, weight, race, lifestyle and other factors play important roles in an individual’s risk for disease. In addition, the presence of a genetic trait linked to HCM or any other disease does not determine that a person will have it.

“It’s less a categorical ‘You have this trait and therefore you will have that disease’ than it increases an individual’s risk profile,” Taylor said.

Tarryn Ford, meanwhile, takes either valsartan or a placebo two times a day and will have a full physical in early June. She says she’s “always felt fine” but is also glad to have gotten a definitive answer about her risk for HCM.

“I have to know,” she said. “I can’t live without knowing.”

She also sees her study participation as valuable for others. “I’m sure there are not a lot of people my age who know to look for this. I know this will help other people.”

 

About the author

Tyler Smith is a freelance writer based in metro Denver.