She’s small for a 6-month-old, but otherwise Avery Gagnon looks perfectly healthy. She smiles, kicks, laughs and grabs her toys and pacifiers. What you’d never know is that Avery has complex congenital heart disease and might not be alive today if it weren’t for an innovative procedure that used mitochondria from her own cells to boost her heart’s energy.
The procedure is the brainchild of James McCully, PhD, a cardiovascular research scientist at the Heart Center at Boston Children’s Hospital, who spent most of his career working to solve a common complication of heart surgery: damage to heart muscle cells.
During certain types of heart surgery, the tissues are temporarily cut off from the body’s oxygenated blood supply. Even after oxygen supply is restored, the heart may remain stunned. The mitochondria within heart cells become dysfunctional and are unable to provide enough energy for the heart muscle to pump as strongly as it should.
Large amounts of damaged mitochondria can be especially challenging for the youngest and frailest cardiac surgery patients: infants with congenital heart disease, like Avery.
Soon after Avery was born in Manchester, New Hampshire, on Dec. 4, 2015, she started suffering seizures and was moved to the neonatal intensive care unit. A heart murmur was detected at her newborn screening and confirmed with a follow-up echocardiogram. She turned out to have complex congenital heart disease, with diagnoses including Shone’s complex, hypoplastic left arch and hypoplastic aortic valve.
“We were already dealing with the seizures, and then this,” remembers Avery’s mother, Jessica Blais. “We were transferred to Boston on Dec. 7; the first few weeks down here were a blur.”
Avery’s disease required multiple open heart surgeries in a matter of months. While she fought off complication after complication, day after day, her heart weakened. Her surgeon, Louis Quinonez, MD, consulted with his colleague Sitaram Emani, MD, who had used the mitochondrial transfer method a handful of times before. Together, they offered the new treatment to Avery’s parents. It would provide an energy boost to her heart using parts of her very own cells, taken from a chest muscle sample.
“Emani was very honest with us,” says Jessica. “He told us that not many patients have had this before. But we understood that the risks were minimal considering the larger risks Avery was facing. We thought, what more harm can it do? We decided to go through with it.”
To harvest the mitochondria, Emani took a small piece of muscle, smaller than a dime, from the bottom of the incision used for Avery’s heart surgery. That cell sample was then taken to a lab where the mitochondria were isolated. While Avery’s heart was still exposed, Emani injected the mitochondria into the damaged areas. The entire process took less than 30 minutes.
“What this does is provide an extra energy source to the heart,” explains McCully. “Over a longer period of time, the mitochondria move into the cells, providing extra function.”
McCully’s animal studies have found that when additional mitochondria are introduced to damaged heart tissue following a heart attack, the animals regain function faster and are more effective at repairing resulting tissue damage.
In 2015, Emani and McCully performed the first mitochondrial transfer in a critically ill child through an Innovative Therapy protocol. That child did not survive, but the procedure saved the life of a second baby who had suffered a severe heart attack and was on heart lung machine support. That child’s heart, which was barely able to function, was revived by the procedure, and she was able to go home to recover.
After Avery’s mitochondrial transfer treatment, on May 1, her heart function immediately improved. A few days later, her heart seemed to weaken, and Jessica began to worry again. But Avery just needed a little more time for the mitochondria to take hold in her cells and for her heart function to catch up. During the following weeks, she grew healthier and healthier.
“I truly think the decision to do this procedure helped. It kick-started the healing,” says Jessica. “I would definitely do it again.”
Avery is out of the ICU and scheduled to go home soon.
Future advances and applications
To date, the mitochondrial transfer treatment has saved a total of three critically ill patients. A clinical protocol will allow the team to offer it to more patients, and 10 will ultimately be enrolled in the first clinical trial.
Doctors and researchers are already thinking about other clinical applications for mitochondrial transplantation.
“We could use this during all major heart operations to speed up recovery,” says Emani. “And after we definitively demonstrate that it works on the heart, we want to expand it to other diseases.”
Possible applications abound, because mitochondrial damage and restricted blood flow contribute to multiple disorders including stroke, Alzheimer’s disease, Parkinson’s disease and rare but devastating genetic conditions.
“We’re now focusing on being able to do this all at the bedside,” Emani adds. “We’re working on a portable unit that can do what we now do in the lab. Ultimately, we want to provide every step of the therapy right there in the patient’s room; it’s one example of how we are constantly striving to bridge the gap between the laboratory and clinic.”
Learn more about the Department of Cardiac Surgery.