Glenn (left to right), Beckham, Cara and Eliza O’Neill pose for a family photo in 2015. Eliza has Sanfilippo syndrome, a rare hereditary disorder.
Robert Clark
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Robert Clark
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When Eliza O’Neill was little, she was one of those kids who always needed to have an accessory, like a hat or a scarf.
“She would always go to the closet for my high heels and step into them — which scared us,” says her mother, Cara O’Neill, a pediatrician in Columbia, South Carolina.
But when Eliza turned 3, her parents noticed she was falling behind in her developmental milestones. She was diagnosed with pragmatic speech delay, meaning she had learned a lot of words, for example, but didn’t use them habitually in social situations.
In 2013, one of Cara’s colleagues suggested testing Eliza for a group of metabolic disorders, just to rule them out.
But the test came back positive for something called Sanfilippo syndrome.
Cara remembers learning about this rare hereditary disease in medical school.
“When they said the word, everything came rushing back,” she says. “And it was just this ball of terror, like, oh, my God, this is horrible.”
Children with Sanfilippo have a defective gene that prevents them from breaking down heparin sulfate, a molecule essential for normal cell function. As it accumulates in the body, it causes serious complications.
Children with Sanfilippo lose the ability to speak and walk. They have seizures and usually don’t make it past adolescence, depending on the Sanfilippo Healing Foundationthat the O’Neills started and continue to run.
For Eliza’s father, Glenn O’Neill, it took some time after learning of Eliza’s test results for the diagnosis to be made.
“It was only when I got home that I realized how quickly the degeneration had happened,” he says. “And that’s really when we said, ‘My God. Whatever we have to do, we have to do it now.'”
Finding treatment
At Nationwide Children’s Hospital in Columbus, Ohio, researcher Haiyan Fu had been working on gene therapy in mice for Sanfilippo since the late 1990s.
The therapy used a modified virus to deliver a working copy of the broken gene to patients’ cells.
Eliza O’Neill receives a kiss from her father, Glenn, before becoming the first person to receive experimental gene therapy for her rare disease in 2016.
O’Neill family
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O’Neill family
Fu realized that the experimental therapy held promise. “And if we treat early, it could potentially cure,” she says. “So I can’t give up.”
Maintaining it – and financing it – was a challenge, however. She thought she would have to stop in 2009. But the families of children with Sanfilippo stopped her.
“They said, ‘You can’t leave. Can we give you some of the funds so you can continue?'” Fu recalled, explaining that these families had helped her from the beginning and didn’t want to see her work stop.
In total, eight patient foundations, including Ben’s dream and a Cure for Kirbycontinued Fu’s work until the research was ready for the first human trial.
Collect money
But a clinical trial would be expensive. Glenn O’Neill had an idea on how to raise money.
“We contacted strangers on a whim that we found on the Internet to make a viral video,” he says, referring to filmmaker Benjamin Von Wong, who I made them a video over a few days in 2014.
It worked.
In spring 2014, the Saving Eliza video helped the O’Neills breaking the GoFundMe record at the time, raising $1 million in just a few weeks. Soon it reached $2 million.
The money raised helped finance the first human trial, which began in May 2016.
The experiments were promising enough for the biotech industry to take notice.
Eventually, a biotech company called Ultragenyx acquired the rights to the gene therapy in 2022 and continued to study it. A few years later, the company submitted its data to the Food and Drug Administration for review.
THE FDA approved gene therapy in September. The unique brew is called Fayuvi.
“The treatment will work better the younger the child, because the more brain is left,” says Emil Kakkis, CEO of Ultragenyx. “By the time they’re diagnosed at 2, 3, 4 years old, they’ve lost a lot of ground. And we’ve treated a few kids as young as 6 months who have done very well. And our view is that when you treat them very young, you actually get better results from gene therapy.”
Ultragenyx has priced the treatment at nearly $4 million, making it the second most expensive gene therapy ever, according to 46brooklyna drug pricing research company.
Kakkis says Ultragenyx is committed to ensuring every patient is treated, regardless of the cost. “There should be no logistical location, site, state or other type of rule that prevents us from caring for the patient. We understand what (we need) to do.”
Moments after the FDA approval was announced, Fu received a call from Cara O’Neill — and messages from other families who funded his research. Some had lost a child along the way.
Fu says Fayuvi’s approval is good news, but it brings him mixed emotions: “It shouldn’t take that long.”
As for Eliza, she is almost 17 now. She was the very first patient to benefit from gene therapy in a clinical trial in 2016.
Because she was 6 years old when she was treated with gene therapy, she had already lost the ability to speak. He never returned, but she can communicate with picture cards and devices. Eliza goes to school. And this summer she swam and learned to float on a pool noodle.
“I just feel proud of my daughter. You know?” Glenn O’Neill says. “I’m proud of her. It’s been a tough road for her, but we also know she’s very lucky.”
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