FOXG1 treatment search: "coincidence after coincidence"

The FOXG1 Research Foundation in the USA has to date distributed a million and a half in funding dollars. The bulk has gone into building mouse models of the disease, led by scientists Soo and Jae Lee. They also happen to also be married, with a daughter who has FOXG1 syndrome. It's interesting but not that surprising - except that that they were neurodevelopmental experts long before their daughter was born. Jae Lee told the story to Phil Sansom...

Jae - I was also studying gene transcription, although in a different context, so when our daughter arrived and then the issue was FOXG1 syndrome... complete coincidence. I mean, we were kind of like really shocked. Another coincidence was that FOXG1 was one of the markers that my wife has been using in her studies, so she was extremely familiar with what the protein was. Kind of like coincidence after coincidence, right? We kind of took it as fate.

Phil - For both of them, it was a natural transition to just start specifically researching FOXG1.

Jae - Almost nothing is known about how FOXG1 functions, so that's why we are creating many mouse models.

Phil - These different models have different types of mutations in the FOXG1 gene. And these mimic the types of mutations you see in humans.

Jae - The spectrum of symptoms are very different because FOXG1 has different domains, functional domains, and some of them are way more important than others.  For instance, the domain that's essential for DNA binding; when FOXG1 syndrome occurs through mutations in this DNA binding, that's going to be really severe symptoms. On the other hand, if you have a mutation in a non-essential domain, the symptoms tend to be milder.

Phil - This is what you see in kids with FOXG1 Syndrome - for example, Jae’s daughter Yuna has milder symptoms than Nicole’s daughter Josie.

Jae - This is a neurodevelopmental disorder, meaning that when children are born, the trouble is already there and you can not go back. And in principle, once the brain is built improperly, it's already done. In the case of FOXG1 syndrome, what we found was that the FOXG1 protein continues to be expressed in adult stages; and FOXG1 protein expressed in adult stages still playing really, really important roles.

Phil - For Jae this was big news. Not only does FOXG1 do its thing in the womb, it keeps on doing its thing. Meaning that fixing a problem will still help. In the case of the mice, if FOXG1 breaks after the little pups are born, their brains still get that characteristic shrunkenness.

Jae - That actually gave us great hope.

Phil - It sounds like you're talking about not just trying to stop FOXG1 syndrome ever occurring, but also trying to look for a cure for kids who already have it.

Jae - Absolutely, absolutely. It's not going to be a complete cure, but I believe that some of the symptoms can be treated. That would make the life of parents much easier.

Phil - It’s not usual to find a scientist with this amount of skin in the game. Jae is trying to find a treatment that will fix FOXG1 in the mice. He’s essentially working on subbing in a spare copy of the gene that won’t sit in the mice’s normal DNA, but instead will hang around inside a modified virus - what’s called a viral vector.

Jae - FOXG1 Syndrome is basically, instead of 100% of FOXG1, you only make 50%, right? So you can actually, using a viral vector that contains the FOXG1 gene - that can make FOXG1 protein - you deliver this viral vector to the patients. So you are trying to recover or restore the normal level of FOXG1 protein. We actually are at exactly at that stage right now. So now we can test whether any of those symptoms can be alleviated. So we are actually at a pretty exciting time to see whether we can do something.