The birth of their first child three and a half years ago completed Natalia and Juan Lovato’s lives. Both from Argentina, Juan was a professional soccer player in Guatemala, where Natalia ran a successful Argentinian restaurant.
Soon, however, they noticed their son Ciro couldn’t hold up his head. Then, they were alarmed that he wasn’t making eye contact.
By the time Ciro was one, they found out he was suffering from Canavan disease – an extremely rare genetic disorder that causes progressive brain atrophy and ultimately leads to death.
“The doctors told us to go home and enjoy being with Ciro because he did not have many years to live,” Natalia said recently.
Yet they weren’t about to give up.
The family got word that a gene therapy trial was being conducted at a hospital in Ohio. When they found out that Ciro would be considered a suitable candidate, the Lovatos sold everything and in May 2022 traveled to Dayton, the western Ohio city of about 136,000 people.
“We didn’t hesitate for a second,” Natalia said.
Canavan disease is caused by mutations in the ASPA gene. It interferes with 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 there is a one-in-four chance that children of carrier parents get the disease.
The Genetic and Rare Diseases Information Center says Canavan disease affects fewer than 50,000 children in the US, but experts say the known number of typical cases is likely to be well under a thousand – perhaps as few as 100.
The life expectancy for children with the disease is about 10 years and involves the gradual degeneration of their health, though clinical trials involving gene therapy have proved encouraging. The first person in the world to receive a 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 have so far received in Dayton involves introducing a vector – a virus that has been modified to eliminate its ability to replicate or cause disease – that delivers DNA into the patient’s brain cells.
“The first kids we treated were up to five years old, so they have already severely degenerated at that point. At that point, there might not even be enough myelin cells to inject and restore function,” said Dr Robert Lober, a pediatric neurosurgeon who has led the clinical trials at Dayton Children’s hospital, the first medical facility to conduct intracranial gene therapy using this particular vector for Canavan disease.
“Those kids have actually had some improvements in terms of function of their myelin and have not had that characteristic drop-off and degeneration and remained stable.”
Ciro’s parents have noted a marked improvement in his health and wellbeing.
“Now he can tell us using sounds that he wants us to change the cartoons – he is almost able to say ‘blue’ when he wants to watch [the Australian animated series] Bluey,” Natalia recounted.
“If he wants something to eat and we give him an option, he’s able to make sounds to tell us which one he wants.”
Lober says that while the gene therapy is experimental rather than a cure or a treatment for the disease, he has seen some families reinvigorated.
“It’s more than just gene therapy,” he said. “You’re giving hope.”
But Canavan disease is so rare – it is sometimes labeled an “orphan disease” – that funding for research and trialing faces major challenges. One gene therapy treatment costs about $800,000.
There’s also the somewhat selective nature of the trial process that means not every child with Canavan disease may be able to participate.
“If there’s a kid that has brain atrophy, doesn’t have any foundational myelin, has high levels of edema, they are probably not going to be eligible for a trial because it probably is not going to work as well,” said Samantha Karlin of the Canavan Research Foundation, whose sister Lindsay was the first to receive gene therapy for Canavan disease.
She said another impediment is that the US Food and Drug Administration has made changes to trial requirements that can cost millions of dollars to implement.
While gene therapy plays an essential part in slowing a child’s degeneration, ongoing physical therapy is crucial.
“I always tell people: getting the gene doesn’t make your myelin. Myelin is activity-dependent. You got to go train like a Navy Seal, you have to go build those pathways,” Lober said. “It’s not just about putting the gene in – they have to do those physical therapies.”
That’s exactly where the Lovatos today find themselves 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 has led Natalia to baking alfajores, Argentinian cookies that she makes at home and sells online – which sometimes keeps her up until 4am.
For now, the Lovatos are living hour to hour, day to day.
Seated in a highchair in a rented apartment outside Dayton, Ciro’s face recently lit up when his mother spread cream cheese on a cracker in front of him. She handed him the snack and, not without effort, Ciro leaned back his head and slowly opened his fingers, releasing the cracker into his mouth.
A smile spread across his face.
