When she’s not making medical history, Celia Grace Hamlett might seem like a pretty typical 5-year-old, playing with dolls and Play-Doh and swinging on the playground.

But this child from Alabama is anything but ordinary. In September, she became the first person in the United States to receive gene therapy for metachromatic leukodystrophy (MLD)—a rare and often fatal genetic disease.

A team led by Paul Orchard, M.D., at M Health Fairview Masonic Children’s Hospital performed the groundbreaking procedure after working with the U.S. Food and Drug Administration (FDA) to get it approved for her.

“We are dedicated to delivering the best care we can and, if necessary, going beyond current care to usher in the future,” says Masonic Children’s Hospital physician-in-chief Joseph Neglia, M.D., M.P.H. “Because of Dr. Orchard and his colleagues, we were first in the U.S. to do this, and we look forward to many new ‘firsts’ in the future.” 

In 2020, Celia Grace was diagnosed with MLD—a progressive neurodegenerative disease—almost by a fluke. When she had her gallbladder removed around age 3, the pathologist found a mass that’s uncommon outside of people who have MLD and recommended a genetic test.

The results knocked Kassie and Gary Hamlett, Celia Grace’s parents, to their knees. 

“My body went numb,” Kassie Hamlett recalls. “I was sick. Gary was, too. We couldn’t even drive ourselves home.”

Their neurologist immediately recommended a new gene therapy, in large part because Celia Grace didn’t yet have symptoms of MLD. Because her disease was still in the early stages, gene therapy was more likely to be successful.

MLD, caused by a missing enzyme, is an inherited disease that primarily affects the brain and nerves. Children who have MLD eventually lose the ability to walk, talk, and interact with the world around them. The disease is fatal if untreated.

Until now, MLD has been treated with a bone marrow transplant, a specialized procedure that the University of Minnesota Medical School has pioneered and fine-tuned over the last five decades. However, transplantation is still a risky procedure associated with a long hospital stay and many possible complications.

Gene therapy is a promising new area of treatment for genetic conditions like MLD. Not only does gene therapy help to prevent symptoms of the disease, but it has the power to cure the condition for good.

Clearing hurdles

The Hamletts were thrilled to pursue gene therapy as an option for Celia Grace. But they faced an immediate—and significant—hurdle.

The gene therapy she needed had thus far only been offered in Italy. But Orchard and his colleagues in Minneapolis wrote a treatment regimen for her, lobbied the FDA, and got clearance to perform the procedure for Celia Grace last summer.

In July, Celia Grace and her family traveled nearly 1,000 miles to Minnesota for treatment. The M Health Fairview team collected stem cells from Celia Grace’s body and sent them to a laboratory in Milan, where the cells were re-engineered to produce the enzyme they were missing. Back in Minnesota, Celia Grace underwent four days of chemotherapy to prepare her body to receive the re-engineered cells.

On September 27, Celia Grace received the gene therapy: more than 500 million re-engineered cells in four IV bags were infused back into her body.

At Celia Grace’s last checkup in January, the Hamletts were thrilled to learn that her enzyme counts were at the high end of the normal range—exactly what they had hoped to see.

Paving a new path

Orchard and his colleagues at Masonic Children’s Hospital will continue to follow Celia Grace for at least 15 years. If the gene therapy does its job and her body continues to produce the critical enzyme that was once missing, there’s a good chance that Celia Grace won’t need any additional therapies. And she’d be considered cured.

“We are so thankful we were led here,” Kassie Hamlett says. “This hospital changed our life.”

Orchard anticipates that Celia Grace will pave the way for other kids with asymptomatic or early-stage MLD to get gene therapy at Masonic Children’s Hospital. In fact, his team has two more kids lined up to receive the therapy in the coming months.

“FDA approval might take a couple of years,” says Orchard, an M Health Fairview blood and marrow transplant physician and University of Minnesota Medical School pediatrics professor. “Until then, we’re going to be the only place in the country able to offer this.”

Philanthropy—from the organizations Chloe’s Fight Rare Disease Foundation, Cure MLD, and the Calliope Joy Foundation, among other sources—has helped to advance the U’s MLD research program.

Generous friends and donors also helped Celia Grace access this new therapy by paying for the costly gene therapy–related safety testing required by the FDA—at a price tag of around $100,000.

“It would be almost impossible to move forward without that funding,” Orchard says. “To do this stuff really takes a village.”