SOMERVILLE — At 19 months old, Lucas Guo has never crawled, walked, or stood by himself. He babbles but can’t say words. He struggles to chew and swallow. He gets most of his nutrition through a feeding tube attached to his belly.
Lucas has one of the world’s rarest diseases, ZTTK syndrome, a complex neurological disorder caused by a genetic mutation. Scientists have documented only about 60 cases worldwide and estimate that, at most, it afflicts several hundred people — far too few to encourage drug makers to find a treatment.
That economic reality has driven Lucas’s parents, Ada Lio and Nathan Guo, to take things into their own hands. Working through a small foundation, they are trying to raise $10 million to develop a treatment or cure for ZTTK in five years.
Lio and Guo each spend about 40 hours a week — on top of their full-time jobs — contacting scientists, venture capitalists, nonprofit groups, and parents of children with other rare diseases for advice, support, and donations. They make their pitches with a polished, professional slide deck that they created, outlining potential approaches to treating ZTTK, including gene therapies and gene editing. They scour the scant scientific literature on the disease — including case studies in Chinese, which both of them speak and read.
“We feel very confident that finding a treatment or a cure for Lucas and other patients is possible,” said Lio. “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.”
The challenges facing Lio and Guo may seem as rare as their son’s disease, but more parents could find themselves in similar straits. The same revolution in genetics that has produced breakthrough medicines is allowing scientists to rapidly discover and pinpoint the causes of baffling diseases — but often without being able to offer treatments.
ZTTK, which was identified eight years ago, illustrates that paradox, 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.
Lio and Guo, both 35, met at the Hong Kong Restaurant in Harvard Square on Saint Patrick’s Day in 2012. (”I approached Nathan, and the rest was history,” Lio said.) They were married eight years later, and not long after that decided to start a family.
Lio’s pregnancy went smoothly. The couple discovered that something might be wrong when she underwent an ultrasound in her 38th week and learned the baby’s body weight was extremely low.
Then hours after Lucas was born in July 2022, he stopped breathing and had to be resuscitated. He spent the first month of his life in the neonatal intensive care unit of Brigham and Women’s Hospital. Doctors didn’t know why he couldn’t nurse or drink formula and wasn’t thriving.
The answer came seven months later when a genetic screening test called whole exome sequencing determined that one of two copies of a gene called SON didn’t function properly. That affected the development of Lucas’s organs and tissues. The genetic mutation is not inherited but occurs spontaneously after conception.
ZTTK is named for the first initials of the last names of four scientists who authored papers about the disease. Physicians still don’t know a lot about the disorder, including whether it is degenerative and shortens lives.
“There’s obviously still a lot we’re learning about this condition,” said Dr. Jessica Martin, Lucas’s primary care pediatrician at Children’s Hospital, who had never before treated someone diagnosed with ZTTK. “We’re learning from Lucas.”
The disease has caused a host of health problems for the boy, including a cleft palate that was surgically repaired, a heart defect, weak muscle tone, farsightedness, and developmental delays. He sees at least 10 specialists at Children’s Hospital as well as doctors at Brigham & Women’s and Massachusetts General Hospital. He has appointments every weekday with therapists assisting him with speech, eating, coordination, and other skills.
Despite his health woes, Lucas, slight and bespectacled, enjoys playing with toys and looking at books, including one that plays a recording of “The Itsy Bitsy Spider.” Wearing braces on his legs, he recently took his first steps after a physical therapist placed him in a four-wheeled walker.
“Oh, my God!” exclaimed Lio, who coaxed her son to take four steps by holding a colorful plastic toy pineapple in front of him in their living room.
“You’re so toy-motivated, Lukie,” quipped Guo.
Guo and Lio consider themselves luckier than other parents of kids with ZTTK. They are familiar with health care, biotechnology, and drug development because of their jobs. He is senior director of corporate strategy at Thermo Fisher Scientific, the Waltham instruments maker that has invested heavily in cutting-edge medical treatments, and she is director of strategy at CVS Health, based in Woonsocket, R.I.
Their employers allow them to work most of the time from their Somerville condominium while they care for Lucas with assistance from a full-time nanny, according to the couple. They have connected with other parents of children with the disease through a Facebook group and the ZTTK SON-Shine Foundation, which those parents helped establish in 2021 and Guo and Lio have joined.
The foundation’s vice president, Kerry Tirrell, whose 3-year-old son, Jack, has ZTTK syndrome, said Guo and Lio have brought “their own unique experiences and networks to the foundation’s work.”
“I’m in favor of anything that brings awareness and research to our community,” said Tirrell, who works as a regulatory lawyer for the New York Stock Exchange and lives in Westchester County, N.Y.
Through their industry contacts, Lio and Guo have enlisted eight researchers to join a scientific board advising the foundation on drug development, including Yu, of Children’s Hospital. Several of the scientists are affiliated with Children’s, the Broad Institute of MIT and Harvard, and Harvard Medical School.
“For anyone else, this would be almost impossible — even just to deal with day-to-day care [of a child with ZTTK], let alone being able to pursue drug development,” said Guo. “We’re in a blessed position to be able to do this. So, we feel an obligation to the community to be able to drive this forward for all of the ZTTK patients.”
Rare diseases have become a big business for drug makers over the past 40 years. Some 7,000 known rare diseases affect between 25 and 30 million Americans — or about one in 10, according to the National Institutes of Health.
In the United States, a disease is considered rare if it affects fewer than 200,000 people. About 95 percent of rare diseases have no treatment, according to the National Organization for Rare Disorders, and most have a genetic cause.
In the past decade or so, drug makers — including some in Massachusetts’s biotech sector — have won approval of ground-breaking treatments for rare disorders, from cystic fibrosis to sickle cell disease. The medicines typically carry extraordinarily high price tags. In 2022, for example, the Food and Drug Administration approved a one-time gene therapy for a form of hemophilia that costs $3.5 million per patient.
ZTTK, however, isn’t just rare — it’s ultra-rare, making it hard to entice any pharmaceutical company to invest millions of dollars in drug development. That’s why Guo, Lio, and the foundation are trying to raise $10 million. So far, the couple has raised more than $150,000, said Lio. The couple is continuing to raise on GoFundMe on behalf of the ZTTK SON-Shine Foundation.
To some, the fund-raising target, not to mention the goal of developing a treatment or cure within five years, may seem unrealistic. Drug development can take a decade or more, and roughly 90 percent of experimental medicines never get approved.
But Dr. Winston Yan, cofounder of Arbor Biotechnologies of Cambridge and member of the foundation’s scientific advisory board, said Guo and Lio’s goals are ambitious but not quixotic.
“I’d never put it past motivated parents and a well-connected family like theirs to actually make it happen,” said Yan, founding president of N=1 Collaborative, a nonprofit group of scientists working on customized treatments for rare diseases. “Sometimes, all it takes is another individual to write one large check.”
And scientists can tout an important step in the effort to treat ZTTK.
Dr. Erin Ahn, an associate professor of pathology at the University of Alabama Birmingham, has led a group of researchers who modified the SON gene in laboratory mice to cause ZTTK, providing animals on which to test potential treatments. Ahn previously led a team of researchers that helped identify ZTTK in 2016.
Like any parent of a child with a serious illness, Guo and Lio said they wondered why Lucas was born with such a devastating affliction. But they remain relentlessly optimistic and don’t dwell on that.
“You’ve just got to keep moving forward,” Lio said.
Jonathan Saltzman can be reached at jonathan.saltzman@globe.com.