For most of his life, teenager Connor Dalby could not walk by himself. As a baby, he experienced 50 to 100 seizures per day, his mother, Kelley Del Real, tells KPBS’ Heidi de Marco. Antiseizure drugs offered little relief. He was not expected to live past his fourth birthday due to his extremely rare genetic mutation, reported Endpoints News’ Jared Whitlock in 2024
Then, at age 14, Dalby received the first dose of an experimental medicine that was developed over three years. After more than a year of the spinal injections, administered a few months apart, Dalby’s seizure frequency fell by an estimated 90 percent. Now, at 17, he can take 50 or 60 steps unassisted, his mother tells KPBS
“It’s totally changed our quality of life and given him certain skills and a level of independence that he did not have before,” Del Real says
Dalby’s improvements are remarkable. But one of the most unusual features of the medicine he took is that it was tailor-made for him
In two parallel clinical trials with results published July 21 in the journal Nature Medicine, researchers tested two drugs: One was designed for Dalby’s genetic profile, and the other for a boy who was 9 at the start of the study and had the same condition caused by a different mutation. The results reveal the potential of what’s called “n-of-one” medicine. If a disease-causing genetic variant is too rare to warrant a conventional trial with many participants, researchers can instead design drugs for the individual patients who need them.
In 2017, Del Real and another parent reached out to Stanley Crooke, then CEO of Ionis Pharmaceuticals, to ask about developing a treatment for their children’s mutations in a specific gene, per Endpoints News. Crooke told them that there were simply not enough patients to warrant a commercial program
But he didn’t forget their request. He later stepped down from Ionis and founded the nonprofit n-Lorem Foundation to create medicines for people with extremely rare genetic mutations
“The question actually shifted for me to a moral question,” Crooke told Endpoints News. “How could I not do it?” N-Lorem ultimately funded and created Dalby’s medicine
Did you know? Personalized medicine
The n-of-one therapies are part of a larger, emerging movement that aims to personalize medicine based on a patient’s genetics. It can apply to the prevention, diagnosis and treatment of disease
Both children in the trials have mutations in the gene SCN2A that cause developmental and epileptic encephalopathy, a severe form of childhood epilepsy that can also lead to developmental delays, movement disorders and gastrointestinal problems. Issues with the gene affect how the brain’s nerve cells communicate with one another
The boys each carry two copies of SCN2A in their DNA: one healthy and one harmful. To combat the faulty copy, scientists created molecules called allele-selective antisense oligonucleotides, or ASOs. The ASOs bind to the genetic messenger associated with the harmful copy, preventing it from being made into a protein, while allowing the healthy one to function normally
Each boy participated in a separate clinical trial and served as his own control. Researchers compared seizure count, medication use and skills associated with brain development before and after treatment
Administered into his spinal fluid roughly every two to three months, Dalby’s ASO was associated with substantial improvements. Along with the drastic decline in seizure frequency, his proportion of seizure-free days rose from zero to 46 percent
The younger participant’s seizure frequency declined by an estimated 26 percent, although that result was not statistically significant. Still, he was able to stop taking a seizure medication that he had needed since infancy
Both children tolerated their medications well, and they didn’t experience any serious adverse events or show any abnormal laboratory or brain analysis results
Dalby’s newfound ability to walk was especially unexpected. It “suggests that there are critical windows of development but that there can be continued brain plasticity,” study co-author OliSan Diego, tells Medscape Medical News’ Megan Brooks
While the results are promising, two cases alone cannot establish how effective or safe n-of-one approaches will be for other patients
“The most powerful conclusion is that neurological problems thought to be irreversible can be reversed,” Paula Río, a gene therapy researcher at Spain’s Center for Energy, Environmental and Technological Research who was not involved in the study, tells El País’ Nuño Domínguez per a translation by Smithsonian magazine
It is not yet clear how long the benefits to the two patients will last. They will need repeated spinal injections to sustain their improvements, because the drugs do not change their DNA
Additionally, a big challenge for the field of tailor-made medicines is how to scale them up into a broader health system. Timothy Yu, a physician specializing in genetic disorders at Boston Children’s Hospital who was not involved in the new study, told Endpoints News that while he was encouraged by progress seen in Dalby’s case and others, he was “starkly aware that it’s not nearly enough.”
Editor’s note, August 4, 2026: Earlier versions of this story misspelled Del Real’s first name
