Researchers take aim at root of deadly genetic disease that's stalked N.L. families for generations
Identifying ARVC gene led to life-saving treatment. Now researchers want to stop disease even sooner
Research in Newfoundland and Labrador led to a treatment that keeps Chad Pelley's heart from stopping, but the genetic variant he carries still poses a long-term threat to his health.
Now, stem cells research aims to solve that problem, too.
"When I was diagnosed, me and my father talked about how one day, maybe in the next generation of Pelley's, people will be doing research to turn off genes or maybe people with our condition could have a drug," said Pelley, who learned he had the genetic variant for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) two decades ago.
"We always thought that would be something one-hundred years from now but, in fact, this is happening here, now."
Pelley, 44, has what's become known as the "Newfoundland curse" — a genetic variant passed through generations of families that causes sudden, cardiac deaths.
'I could just feel my heart fluttering, like my heart was a bird trapped in a cage trying to get out.'- Chad Pelley
"My grandmother passed away suddenly and was relatively young, and there was talk of a cousin on that grandmother's side who died young and nobody understood why," he said.
Pelley had unexplained episodes himself, that in retrospect were likely evidence of his potentially deadly genetic makeup.
"Before I knew I had it, I was doing a strenuous hike to a place called Crippled Cove. I was one of the last to leave. So I kind of ran up the mountain and I could just feel my heart fluttering, like my heart was a bird trapped in a cage trying to get out," he said.
About a year later he told researcher Dr. Kathy Hodgkinson about the event. Hodgkinson is a member of the Memorial University team that identified the genetic variant that caused ARVC.
"I was always curious what that was, and later speaking with Kathy I shared that with her and her eyes opened wide, like she knew that could have been a fatal incident," Pelley said.
By the time Pelley was in his twenties, there were already some answers.
Genetic researchers at MUN had identified the genetic variation that caused those deaths.
Pelley and his family also had a blood test to determine exactly who had the variation.
"So my father had the blood test, I had the blood test, my brother had the blood test, and we found out that we had it," said Pelley.
People with the genetic variation have arrythmias, irregular heartbeats, and sometimes their hearts stop beating altogether. But once someone knows they have it, there is a way to control it.
Pelley, and about 300 other people in Newfoundland and Labrador, have had defibrillators surgically implanted in their bodies. Those devices keep their hearts from stopping.
"The statistics are that by the age of 40 someone with this variant would have had a sudden cardiac episode, possibly died, if they didn't have a defibrillator put in. So I'm one of the lucky ones," he said.
But he's not out of the woods yet.
Possible heart transplant
Even after a defibrillator has been surgically implanted, the genetic variant still poses a deadly threat. For some carriers, the irregular heart beats, or arrhythmias, caused by the variant get so bad that they need a new heart.
"Some of our people get heart transplants because their arrhythmias are so bad that their defibrillators are going off every half an hour. You can't live with a defibrillator going off every half an hour. So that's an unusual presentation for transplant," said Hodgkinson.
Living with the variation can also lead to another problem — one that Pelley's father had.
"As you age with this disease, your heart muscle can turn to fat instead of muscle and doesn't pump. That happened to my father who had to have a heart transplant and other people in my family," Pelley said.
"So I know that that's potentially in my future."
Heart cells beating in a Petri Dish
Memorial University's Dr. Jessica Esseltine hopes to play a role in rewriting that future.
With stem cell research she's trying to find the root cause of ARVC she hopes will lead to a treatment that will prevent the disease from developing altogether.
The first step is understanding exactly what the gene variant does to a carrier's heart.
"We don't know how this gene change actually compromises the heart muscle function. So that's where I started trying to understand why this gene change causes our hearts to either stop spontaneously or causes the muscle to fail, requiring heart transplant," she said.
Esseltine is taking skin cells from people who have the variant, and those who don't, and turning them into heart cells. The cells actually beat in the petri dish.
"Unfortunately, it's very difficult to get a piece of someone's heart. I certainly wouldn't give a researcher a piece of my heart, but it's really easy to get a piece of their skin or their blood," she said.
"So using a Nobel Prize winning technique, we can change a person's skin into heart. So then we can look in the lab to see what's different about an ARVC heart cell versus their unaffected brothers and sisters."
The ARVC heart cells contract irregularly, whereas the heart cells from people who don't have the variant beat regularly.
The long-term goal is even more ambitious.
"Of course researchers would love to find a cure. There's a couple different avenues. We could use gene editing to repair the mutation in a patient's heart or we could use regenerative medicine involving stem cells to regrow or replace damaged tissue in the body," said Esseltine.
She believes it's more likely a drug therapy will come first.
"That would still be just treating the disease. From my view, the only way to cure it would be the gene editing, which is still in its infancy," said Esseltine. "I think it could possibly take my whole career, but, you know, science happens either incrementally or in massive breakthroughs, so we're always hopeful that we'll have a massive breakthrough at any moment."
For people, like Pelley, who live with the dire possibilities the gene variation can lead to, this latest update holds great promise.
"This story already had an amazing ending," he said.
"We found out what the Newfoundland curse is. A blood test was developed to find if you had it and now you can put an implanted cardiac defibrillator to keep you safe. That's enough. That's a happy ending there. But the fact that we're now talking about turning off this gene or developing drugs that could reduce the impacts of it on your heart, is just a new wave of relief or hope."
That hope is for a time when people with the genetic variant won't need defibrillators or heart transplants, said Pelley.
"Like every 10 or 15 years I have to have my defibrillator taken out to change the batteries. So now I'm wondering, if in 2036, will I have to have this taken out to have the batteries changed or will we just remove the device because there's a cure for ARVC?"
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