Twist of fate leads scientist on a quest for a cure
The birth of American geneticist Soo-Kyung Lee’s daughter Yuna changed not only the scientist’s personal life, but launched her career as the world’s foremost scientist researching FOXG1.
As American scientist Soo-Kyung Lee settled in at home with her newborn baby Yuna, it was clear fairly quickly to the developmental biologist and neuroscientist that something wasn’t right.
“What we noticed was that Yuna cried a lot,” Dr Lee says. “Day and night, Yuna cried and she didn’t sleep much. When we took her to clinics, we were told ‘some babies just cry a lot’. But then we noticed that her head circumference was not growing at the typical speed, and then she started to have seizures.
“We got MRI analysis done on her brain. And it turned out there were some structural abnormalities, which ultimately led to the identification of FOXG1 syndrome.”
FOXG1 syndrome is a neurodevelopmental condition caused by not having enough of a critical functional protein in the brain. If a child has a mutation on one of the FOXG1 genes, the brain does not make enough of this protein and it profoundly affects brain development. Children who suffer the condition typically experience major developmental disabilities and usually never walk or talk. They also often have cortical vision impairment and cannot focus or connect with loved ones’ faces.
Investigations into Yuna’s genetic disorder – she is now 14 – were occurring before FOXG1 had even been described as a syndrome, which happened in 2011. The condition is so rare that there are only about 1100 documented cases so far worldwide, but diagnosis rates are accelerating.
Yuna’s mum was performing genetic research on mice of a different nature, but her daughter’s birth not only changed the scientist’s personal life, it also launched Dr Lee’s career as the world’s leading scientist researching FOXG1. She is now on a mission to create a gene therapy.
“Since I had this background already as a geneticist, and then finding out that my daughter has the FOXG1 gene mutation, it was very natural that I changed the main target of my research to FOXG1,” Dr Lee tells me from Buffalo University, where the FOXG1 Research Center will open in the new year. It will be the world’s first institute devoted to the condition, thanks to the work of Dr Lee and her neuroscientist husband Dr Jae Lee, who works with his wife side-by-side. The university unashamedly proclaims that the research centre is born of hope and love, not just the pursuit of cutting-edge science.
“This research centre really represents a bold step forward, not only for the University of Buffalo, but for the future of science,” the university’s science dean Robin Schulze said at the centre’s recent launch. “It means we are that much closer to finding a cure for the neurodevelopmental disorder FOXG1 syndrome.”
My family is hanging on the progress of Dr Lee’s gene therapy, because my sister’s firstborn daughter, Josie, also has FOXG1. Yuna has a shock of black hair, Chinese heritage and is two years older than Josie, but looking at videos and photographs of Yuna, the likeness with my blonde, fair-skinned niece is uncanny. The way they move; the way they reach to strike the keys of a piano; their smiles that tell their loved ones they feel a connection, even though they can’t speak or focus with their eyes, are exactly the same in every way. It’s almost spooky.
My sister, Sara, is hoping Josie might be able to join Dr Lee’s clinical trial if it extends to Australia. Names of children with FOXG1 syndrome in Australia have already been gathered as the first step in the process of expressions of interest. Dr Lee hopes to start clinical trials in the US in 2026.
Dr Lee’s research is in its very early stages – she’s currently injecting mice with a therapy that contains a virus that enters the brain and triggers the cells to produce more of the critical functional protein that is lacking in FOXG1 syndrome. But the results have been encouraging so far.
“We are pretty close to making a therapy available for FOXG1 syndrome,” Dr Lee tells me over Zoom from the US. “We are currently doing efficacy tests and toxicity tests in mice, and we’ll progress to toxicity tests in monkeys soon. We will then apply to the FDA to do a clinical trial.
“There are a lot of steps we still have to go through, but I’m very hopeful. I don’t know what would be the exact outcome when we try this in human patients, but I tell the parents that if I’m not convinced to inject this drug into my daughter, I’m not going to pursue this drug for other children.
“One question I get a lot is whether we’ll be able to affect the deficiencies in the brain when children have already grown. What really surprised us and made me hopeful from our experiments is that when we delivered the function gene after birth in mice, even at adolescent stage, we were able to repair a lot of things, beyond what I realistically expected.
“After the virus injection, mice show better cognition ability, which makes me think we can increase communication skills, which would be a huge deal for FOXG1 children.”
As a health reporter, I usually avoid reporting on such early research, because there are no guarantees, far from it, and a huge proportion of early stage research does not progress to the clinic, and as reporters we are careful not to raise patient hopes too early. But I’m drawing an exception here. Because this is emerging genomic medicine in action, it’s a whole new scientific horizon, and this is where it starts. And for my family, for Josie, hope is a lot. It is everything.
