At one and a half years old, most toddlers would be walking, starting to speak and eating by themselves.
But at 19 months old, Lucas Guo has never crawled, walked or even stood up by himself. He makes noises but cannot say words, and finds it difficult to chew and swallow so he gets the majority of his food through a tube attached to his stomach.
The Massachusetts boy has one of the rarest diseases in the world, ZTTK syndrome, which has only 60 reported cases and is estimated to affect – at most – several hundred people across the globe.
The complicated neurological disorder caused by a spontaneous genetic mutation can lead to seizures, autistic behavior and slow development. There is no projected life expectancy.
And because so few people have it, there is little incentive for drug makers to invest hundreds of millions of dollars to search for a treatment – leaving sufferers without any help.
Hours after Lucas was born in July 2022, he stopped breathing, and had to be resuscitated
Lucas spent the first few weeks of his life in the neonatal intensive care unit of Brigham and Women’s Hospital
Lucas’s parents, Ada Lio and Nathan Guo, have decided to take things into their own hands, and are trying to raise $10million to develop a treatment or cure in the next five years.
So far, they have raised more than $150,000.
The pair spend roughly 40 hours a week, on top of their full-time jobs, reaching out to scientists, investors, nonprofit groups, and parents of children with other rare diseases for advice, support and donations.
‘We feel very confident that finding a treatment or a 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 the understanding.’
In appealing to potential donors, they give a presentation explaining potential approaches to treating ZTTK, such as gene therapies and gene editing.
And to learn more about the disease and research a potential treatment or cure, the parents comb through the very limited scientific literature on ZTTK, including case studies from all over the world.
Since its discovery less than a decade ago, physicians have learned very little about the condition, including if it will shorten Lucas’s life.
It has already caused him a multitude of health issues, however, including a cleft palate that he had surgically repaired, a heart defect, weak muscle tone, farsightedness and developmental delays.
He sees more than 10 specialists with appointments every day of the week, as well as therapists that help him with speech, eating and coordination.
ZTTK was only discovered in 2016, said Dr Timothy Yu, a neurologist and genomics specialist at Boston Children’s Hospital, who is advising Lio and Guo.
‘We are discovering genetic syndromes faster than we can generate understanding about them,’ he said.
Guo and Lio are attempting to raise $10 million, having raised more than $150,000 so far
Hours after Lucas was born in July 2022, he stopped breathing, and had to be resuscitated.
He spent the first few weeks of his life in the neonatal intensive care unit of Brigham and Women’s Hospital.
Doctors initially couldn’t work out why he was having difficulty being breast fed or drinking formula.
Suspecting something was wrong, they did a genetic screening test seven months later, known as whole exome sequencing, which showed that one of two copies of a gene called SON did not work properly in Lucas.
This would have impacted the development of his organs. The genetic mutation is not inherited but happens spontaneously after conception.
Scientific literature has shown that mutations in the SON gene cause ZTTK’s symptoms.
The condition got its name from the last names of four scientists who wrote papers about the disease – Zhu, Tokita, Takenouchi and Kim – in 2023.
While breakthroughs in genetic science have allowed researchers to pinpoint the causes of rare and complex diseases, often they cannot offer treatments.
In the US, a disease is categorized as rare if it affects less 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.
ZTTK, however, is not just rare, but super rare, meaning pharmaceutical companies are unlikely to invest the hundreds of millions of dollars it takes to develop treatments.
Research for a new drug begins in the clinic, where scientists undergo lab and animal testing to ensure safety of a therapy in humans.
Some take hundreds of millions of dollars to develop and sometimes require decades-long investment for clinical trials.
‘There’s obviously still a lot we’re learning about this condition [and] we’re learning from Lucas,’ said Dr Jessica Martin, Lucas’s primary care pediatrician at Children’s Hospital, who had never treated someone diagnosed with ZTTK before the little boy became her patient.
