by The birth of their first child three and a half years ago ended Natalia and Juan Lovato’s life. Both from Argentina, Juan was a professional soccer player in Guatemala, where Natalia ran a successful Argentinian restaurant.
Soon, however, they noticed that their son Ciro could not hold his head up. Then, they were afraid he wasn’t making eye contact.
By the time Ciro was one, they discovered he was suffering from Canavan disease – an extremely rare genetic disorder that causes progressive brain atrophy and eventually death.
“The doctors told us to go home and enjoy being with Ciro because he didn’t have many years to live,” Natalia said recently.
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But they weren’t about to give up.
The family received news that a gene therapy trial was underway at a hospital in Ohio. When they learned that Ciro would be considered a suitable candidate, the Lovatos sold everything and in May 2022 they traveled to Dayton, a western Ohio city of about 136,000 people.
“We didn’t hesitate for a second,” said Natalia.
Canvan disease is caused by mutations in the ASPA gene. It affects the body’s production of myelin, the insulating layer around nerve fibers in the brain. Over time, it destroys normal brain development.
Both parents must be carriers of the gene. And the children of carrier parents have a one-in-4 chance of getting the disease.
The Genetic and Rare Disease Information Center says Canvan disease affects fewer than 50,000 children in the United States, but experts say the number of known typical cases is likely well under a thousand — perhaps as few as 100.
Life expectancy for children with the disease is about 10 years and is associated with a gradual decline in their health, although clinical trials involving gene therapy have been encouraged. The first person in the world to receive gene therapy in a trial, in 1996, was Lindsay Karlin, who lived until she was 27 years old.
The one-time gene therapy that Ciro Lovato and nine other children in Dayton have received so far involves the introduction of a vector – a virus modified to eliminate its ability to replicate or cause disease – that delivers DNA into in the patient’s brain cells.
“The first children who were treated were up to five years old, so they’ve really deteriorated at that point. At that point, there may not even be enough myelin cells to inject and restore function,” said Dr. Robert Lober, a pediatric neurosurgeon who led the clinical trials at Dayton Children’s hospital, the first medical facility to perform intravenous gene therapy using this specification. Vector for Canaan disease.
“Those children have actually made some improvements in terms of their myelin function and they haven’t had that characteristic drop and degeneration and they’ve remained stable.”
Ciro’s parents noticed a significant improvement in his health and well-being.
“Now he can tell us using sounds that he wants us to change the cartoons – he can almost say ‘blue’ when he wants to watch it. [the Australian animated series] Bluey,” said Natalia.
“If he has something to eat and we give him a choice, he can make sounds to tell us which one he wants.”
Lober says that while gene therapy is experimental rather than a cure or treatment for the disease, he has seen some families recover.
“It’s more than just gene therapy,” he said. “You are giving hope.”
But Canvan disease is so rare – sometimes called an “orphan disease” – that research and trial funding faces major challenges. A single gene therapy treatment costs about $800,000.
There is also the selective nature of the trial process which means that not all children with Canaván’s disease will be able to take part.
“If there’s a child with brain atrophy, no underlying myelin, high levels of edema, they’re probably not going to be eligible for a trial because it’s probably not going to work as well,” said Samantha Karlin . the Canavan Research Foundation, whose sister Lindsay was the first person to receive gene therapy for Canavan disease.
Another obstacle, she said, is that the US Food and Drug Administration has made changes to trial requirements that could cost millions of dollars.
While gene therapy plays a vital role in slowing a child’s degeneration, continued physical therapy is critical.
“I always tell people: getting the gene is not the same as your melanization. Myelin is activity dependent. You have to get on the train like a Navy SEAL, you have to build those trails,” Lober said. “It’s not just about putting the gene in – they have to do those physical therapies.”
That’s exactly where the Lovatos are today facing a new obstacle.
While the family has received help from the Cure Canavan Fund, they have been hard at work raising money to pay for a trip to Chicago this month for Ciro’s intensive dynamic movement intervention (DMI) therapy – a technique that helps children with motor delays with posture. and balance.
That was caused by Natalia baking alfajoresthe Argentinian cookies she makes at home and sells online – which sometimes keeps her up until 4am.
For now, the Lovatos are living moment by moment, day by day.
Sitting in a high chair in a rented apartment outside Dayton, Ciro’s face lit up recently when his mother spread cream cheese on a cracker in front of him. She handed him the snack and, without effort, Ciro tilted his head back and slowly opened his finger, dropping the cracker into his mouth.
His smile spread across his face.
