When Vivek and Monika Singha welcomed into the world their fourth child, Kushagra, it didn’t take them long to notice something was amiss. Their first son had been attempting to walk at 10 months but for Kushagra, or Kush, within six months he still wasn’t able to roll over or crawl. When his parents tried to make eye contact, baby Kush would often stare off elsewhere, which at first made them suspect autism. Then the seizures started.
“Two days before his first birthday, he had a big seizure, then two months later he developed the infantile spasms, which lasted from when he was 14 months until around 21 months. That was a very rough time for us,” explains Vikek and Monika. Kush was put on medication for child epilepsy, which the paediatrician said should stop the seizures within two weeks, but it wasn’t until eight months later that they began to ease.
After a few more months and more than 75 medical tests, Kush was officially diagnosed with FoxG1 syndrome – a very rare genetic condition characterised by impaired development and structural brain abnormalities, meaning affected children struggle to walk, eat or talk. The relief at having a diagnosis was short-lived however, when internet searches showed there was little awareness around the condition. Kush was in fact the first child in Sydney to be affected by the disorder, and only the 159th in the world.
THE GLOBAL SEARCH BEGINS
The Singhas are not a family to rest on their laurels, and immediately began contacting every specialist or researcher they could – from oncologists, immunologists and geneticists, to biohackers and computational biologists – and in doing so drawing up a research roadmap for finding a cure.
Throughout their global search, they also discovered the US-based FoxG1 Foundation, and decided to set up their own arm of the foundation here in Australia. Their search finally came to an end nine months later after a telephone conversation with Dr Fabien Delerue, a UNSW Medicine researcher.
“I received a call from a father who told me about his son’s condition and explained how he had been in touch with scientists worldwide but could not get any research started,” says Dr Delerue. “The story sounded as confronting as it was exciting and challenging. The main reason he contacted me was because when it comes to rare genetic disorders, the first step is to create an animal model of the disease, and this was precisely what I had specialised in for the last 20 years.”
From there, they set up a small research team that includes UNSW’s Head of the Dementia Research Unit Professor Lars Ittner and PhD candidate Daniel Tan. This latter position was financed by the Kushagra Singha FoxG1 PhD Scholarship, which the Singhas and Dr Delerue tirelessly raised funds for, through everything from Bunnings barbecues and family fun runs to riding 1,000km around New South Wales.
“Before, nobody was fundraising for FoxG1, and now we’ve managed to raise about $100,000 for this research,” says Vivek. “If we can raise more funds, we can continue to scale up progress in this area.”
The research team is working on identifying ways to correct the damaged gene, while a breakthrough in gene editing technology known as CRISPR has brought more hope to the family for its ability to deliver more accurate, faster and cost-effective gene editing. However, because the FoxG1 gene is located in the brain, they must first develop a vector that can safely cross the blood-brain barrier.
While working so closely with the Singhas in his research efforts has been a wonderful and rewarding experience, Dr Delerue says it can be very challenging when things don’t go according to plan. “Research is about troubleshooting, so as much as we want to be accountable for the hope and trust people put in us, we cannot always guarantee that we will be able to fulfil their expectations.”
“Earlier, there was a point of reflection where we thought, this might not work, so is it worthwhile doing all of this?” Vivek adds. “We want Kush to be able to run around on the beach like the other kids, but we think that even if his trajectory only moves slowly upwards, where he could one day walk on his own, that would still be a great improvement for him. The whole process will be a learning curve, so long-term research will be useful.”
A RAY OF HOPE
Though FoxG1 syndrome has since become a standard test on the epilepsy panel, to date only 332 people in the world have been diagnosed with the condition. Vivek and Monika say they have come in contact with at least four other children diagnosed with FoxG1 syndrome in Australia, including one mother whose son is now in high school, able to use a standing frame and interact with the other kids.
“She said that her son was exactly like Kush when he was younger, but he grew out of a lot of it. That was really encouraging for us to know – that though this was hitting Kush really hard at the time, he had a ray of hope,” says vivek. Since then Kush has been able to slowly adapt to using a standing frame, and is showing some progress in his ability to balance. “He’s trying his best, and visually where before his eyes wouldn’t focus, if you hold his iPad in front of him now, he just latches on to it, so that is a big deal,” he adds.
Dr Delerue says that everyone who has donated towards FoxG1 research should be commended for their kind support. “I really want to let them know that their support makes a tangible difference in FoxG1 patients by genuinely providing us with what we need to try and find a cure.”