In 2022, an East Hampton mother learned that her son had a rare genetic condition.
He had been diagnosed with global developmental delay as a child, and was enrolled in special education programs throughout his schooling. He learned to read and speak, and was very social, but persistent cognitive issues — including trouble with focus, memory, and executive functioning — made it difficult for him to complete certain tasks.
When he was in his early 20s, after multiple misdiagnoses, a doctor suggested whole-genome sequencing to determine whether there might be a genetic cause. The results identified a mutation of a gene called Transportin-2 (TNPO2), which is involved in neurodevelopment.
“All of a sudden we find out, this is why. So it was a relief for us to know there was something,” recalled the mother, who asked to remain anonymous to protect her son’s privacy. “We know whatever we did while he was growing up was all we could have done, and our goal now is for him to live an independent life.”
A Google search for “TNPO2” led her to a Facebook group named for the gene. “We are a closed group of parents and caregivers of children with TNPO2 gene disorder,” the description read. “We want to contact other families and share information.”
The group was created in 2018 by Andrea Messina, a Miami mother and advocate. Her daughter, Vera, was the first child diagnosed with a TNPO2-related disorder, after what Ms. Messina described as eight painful years searching for an answer.
Ms. Messina, who is originally from Argentina, was working in Colombia when Vera was born, and recognized that “something was off” soon after they got home from the hospital. The newborn appeared to be healthy, but wasn’t moving or eating, and never cried. When Ms. Messina reported her concerns to the pediatrician, though, the doctor suggested she was experiencing postpartum depression.
“She told me, ‘Every mom complains that the baby’s crying, and you’re complaining that she’s not crying.’ But in my gut,” Ms. Messina said, “I knew there was something wrong.” She and her husband started consulting specialists, and when Vera had her first seizure, “someone finally said, ‘Okay, maybe you’re right.’ ”
Vera was ultimately diagnosed through the Undiagnosed Diseases Network, a U.S.-based research program funded by the National Institutes of Health. After a prolonged application process, the family traveled to the program’s clinical site at Duke University and, when Vera was 8 years old, they were told she had a TNPO2 mutation.
“Of course, the first thing I did was Google it, and there was nothing.” Ms. Messina said. “I opened Facebook and said, ‘Okay, if somebody gets the same diagnosis, they will do the same thing I’m doing, right? Somebody will find me.’ ” It would be nearly two years before a second member joined, and another year before the first research paper about TNPO2 mutations was published in 2021.
The TNPO2 Facebook group has since grown to include parents and caregivers of about 30 children around the world with diagnosed TNPO2-related conditions. The children have different abilities — some cannot walk or speak, some are able to read and write — but many experiences overlap. “Even if you don’t ever meet them in person, you feel a connection, and that’s what I was looking for,” Ms. Messina said. “And sometimes, somebody has an idea that other parents didn’t have, and it could be helpful.”
“Andrea was the parent of the first child to get this diagnosis, and she was the one who was really motivating a lot of the researchers who published that first paper,” said Yiwei She, a Setauket mathematician and machine learning scientist. Her son, Leo, was born two months after that paper was published, and he was diagnosed with a TNPO2-related disease when he was just 4 months old.
“The biggest indicator that something was wrong was when he had a seizure when he was two-and-a-half months old,” Ms. She said. “And he had this condition called microcephaly, which means that his head wasn’t as big as it should be.” The family was able to get Leo into a clinical trial at Boston Children’s Hospital for infants with epilepsy, which gave them access to genetic sequencing. His TNPO2 mutation was identified, but next steps were unclear.
“We weren’t getting much of anything in the way of answers from the traditional medical system, so I had been looking into the research community, trying to figure out the best plan moving forward,” Ms. She explained. “The sooner you intervene, obviously, the better, when it’s a developmental disease. When Leo was born the doctors didn’t notice anything, and then over time, as the disease affected him more and more, the opportunity for improving his condition grew less and less.”
Over the next year, Ms. She drew on her background in research — and well over $1 million in personal savings — recruiting and working with a group of researchers and companies to create an experimental, individualized therapy to target Leo’s condition. Through the process, she recognized that the tools and protocols they were developing through trial and error could benefit other children in Leo’s situation, which inspired her to establish the TNPO2 Foundation.
The mission of the foundation is twofold: to continue work on Leo’s therapy, and to establish pathways to help other families navigate the uncharted terrain of ultra-rare disease treatment. For a single patient, the process of creating a custom therapy, and getting U.S. Food and Drug Administration approval, is incredibly cost-prohibitive and time-consuming. Considering those individuals as part of the broader population of ultra-rare disease patients and building on past data lowers costs and increases access for families with fewer resources.
In 2024, the foundation launched Project Baby Lion, which aims to create scalable solutions to accelerate the diagnosis and treatment of ultra-rare conditions. Its first initiative, a pilot program at Stony Brook Children’s Hospital, sponsored rapid whole-genome sequencing for seven babies in the neonatal intensive care unit. One baby was removed from the do-not-resuscitate list as a result, after sequencing ruled out his “most hopeless” potential diagnoses, and he was transferred to a higher-level NICU for intensive treatment. A few months later, he was able to go home.
“We were really lucky to have known people who were already connected to Boston Children’s, that helped us connect with that clinical trial,” Ms. She said, which resulted in a relatively early diagnosis and the chance to intervene in the progression of Leo’s disease. And while rapid whole-genome sequencing is used regularly in well-resourced hospitals in New York City, and covered by some private insurers, it is still not widely accessible across the state.
A bill, S9638/A1977, introduced in the State Senate would authorize Medicaid coverage of the testing, which Ms. She hopes to see passed. “It is covered in 14 other states, so it’s a bit surprising that New York is so far behind,” she said. “The thing that’s crazy is that it saves Medicaid money. Instead of paying for 100 NICU nights, do this test, get to the right intervention, and get the baby out the door in 10 nights.”
Leo, now 4 years old, has made “modest but noticeable progress,” and the development of Leosen, his eponymous therapy, continues. The foundation has published portions of the New Drug Application it submitted to the F.D.A. on its website, providing a template for families and organizations pursuing similar treatment plans.
“The goal of these interventions is to improve quality of life for these children,” Ms. She said. “But our most ambitious goal is for the children to be healthy again.”
