Our 19-month-old son has a brain disease, so rare drug manufacturers don’t want to develop a treatment… so we’re raising $10 million to find a cure

By the age of one and a half, most toddlers were already walking, talking and eating on their own.

But at 19 months old, Lucas Guo has never crawled, walked or even stood on his own. He makes sounds but cannot say words, and finds it difficult to chew and swallow, so he gets most of his food through a tube attached to his stomach.

The boy from Massachusetts has one of the rarest diseases in the world, ZTTK syndrome, of which only 60 cases have been reported and is estimated to affect at most several hundred people around the world.

The complicated neurological disorder caused by a spontaneous genetic mutation can lead to seizures, autistic behavior and slow development. There is no expected life expectancy.

And because so few people have it, there is little incentive for drug makers to invest hundreds of millions of dollars in finding a treatment, leaving patients without any help.

Lucas spent the first weeks of his life in the neonatal intensive care unit at Brigham and Women’s Hospital

Lucas’ parents, Ada Lio and Nathan Guo, have decided to take matters into their own hands and are trying to raise $10 million to develop a treatment or cure over the next five years.

So far they have raised over $150,000.

The pair spend about 40 hours a week, in addition to their full-time jobs, reaching out to scientists, investors, nonprofits and parents of children with other rare diseases for advice, support and donations.

“We are confident that finding a treatment or cure for Lucas and other patients is possible,” Ms. Lio told the Boston Globe.

“What we’re trying to do is bend the time curve by working hard with scientists and other collaborators in this ecosystem to accelerate understanding.”

To appeal to potential donors, they will give a presentation explaining possible approaches to treating ZTTK, such as gene therapies and gene editing.

And to learn more about the disease and investigate a possible treatment or cure, parents are scouring the very limited scientific literature on ZTTK, including case studies from around the world.

Since its discovery less than a decade ago, doctors have learned very little about the condition, including whether it will shorten Lucas’ life.

However, it has already caused him a host of health problems, including a cleft palate which he surgically repaired, a heart defect, poor muscle tone, farsightedness and developmental delays.

He sees more than 10 specialists with appointments every day of the week, as well as therapists who help him with speech, eating and coordination.

ZTTK wasn’t discovered until 2016, says Dr. Timothy Yu, a neurologist and genomics specialist at Boston Children’s Hospital, who advises Lio and Guo.

“We are discovering genetic syndromes faster than we can generate understanding about them,” he said.

Guo and Lio are trying to raise $10 million after raising more than $150,000 to date

Hours after Lucas was born in July 2022, he stopped breathing and had to be resuscitated.

He spent the first weeks of his life in the neonatal intensive care unit at Brigham and Women’s Hospital.

Doctors initially couldn’t figure out why he had trouble breastfeeding or drinking formula.

Suspecting something was wrong, seven months later they performed a genetic screening test known as whole exome sequencing, which showed that one of the two copies of a gene called SON was not working properly in Lucas.

This would have affected the development of his organs. The genetic mutation is not inherited, but happens spontaneously after conception.

Scientific literature shows that mutations in the SON gene cause the symptoms of ZTTK.

The condition takes its name from the surnames of four scientists who wrote papers on the disease in 2023 – Zhu, Tokita, Takenouchi and Kim.

Although breakthroughs in genetic science have allowed researchers to identify the causes of rare and complex diseases, they often cannot provide treatments.

In the US, a disease is categorized as rare if it affects fewer than 200,000 people.

According to the National Organization for Rare Disorders, 95 percent of rare diseases have no treatment and the majority have a genetic cause.

However, ZTTK is not only rare, but super-rare, meaning that pharmaceutical companies are unlikely to invest the hundreds of millions of dollars needed to develop treatments.

Research into a new drug begins in the clinic, where scientists undergo laboratory and animal testing to ensure the safety of a therapy in humans.

Some cost hundreds of millions of dollars to develop and sometimes require decades of investment for clinical trials.

“There’s clearly still a lot we’re learning about this condition (and) we’re learning from Lucas,” said Dr. Jessica Martin, Lucas’ pediatrician at Children’s Hospital, who had never treated anyone diagnosed with ZTTK before the little boy fell ill became. her patient.