Finding cures for children's genetic diseases

News

Family crowd-funding for gene therapy

19/Dec/2019  

Charlie and Mira Taouk’s hopes for their daughters are quite different from the kind most parents have for their children.

The Taouks wish eight-year-old Mary and four-year-old Neveah could stand and walk without help. They dream that their girls might one day learn to communicate with basic gestures. “At least then they could point to where their pain is,” Charlie says. “If they were hungry or thirsty or tired, they could let us know and we could help. For us, those things would be huge – life-changing.”

Charlie and Mira try to keep their dreams modest. They dare not imagine a cure will be discovered for their daughters’ rare genetic disorder. They don’t even hold out much hope for a decent night’s sleep; seizures regularly rack their girls’ bodies in the small hours. “It’s been years since we went to bed with minds clear of anxiety and panic,” Charlie says.

Mary and Neveah were both born with a mutation in the gene known as PGAP1. It’s a recently discovered disorder so rare it has no name. Charlie and Mira know of no other cases in Australia. Specialists have identified perhaps a dozen cases around the world.

For years it seemed no-one could help Mary and Neveah but now, with support from a donation from the Taouk family and a newly launched crowdfunding campaign, researchers at the University of Sydney and the Children’s Medical Research Institute will work to develop the world’s first gene therapy targeting the PGAP1 mutation. This research is Charlie and Mira’s first glimpse of hope since their eldest daughter started showing symptoms as a baby.

For the first six months of her life, Mary seemed like a healthy little girl. Charlie and Mira first suspected something was wrong when she started missing developmental milestones. Their baby never made eye contact. She cried all the time. She slept no more than three hours a night.

As Mary grew, so did her problems. She could not speak and struggled to eat. Her muscles were so weak it was hard for her to move. She started having seizures – often clustered with only a minute’s rest between fits.
Doctors ran tests, but they came back clear. Without a diagnosis, there was nothing anyone could do.

The uncertainty made it difficult to predict what would happen if Charlie and Mira had another child. At worst, geneticists told them, there was a one in four chance the condition would appear again. That meant there was a 75 percent chance they would have a healthy child. They took the risk.

When Neveah was six months old, familiar symptoms began to appear. Both girls, it seemed, had the same unknown condition. With both children requiring constant care, Charlie gave up his waterproofing business to stay home with his family. “But what can you do when you don’t even know what’s wrong with your child? You can’t even try to help,” he says.

At last, when Mary was seven and Neveah three, new developments in whole-genome sequencing enabled specialists to identify the disorder. The diagnosis gave the Taouks information but not hope. They knew what the problem was, but there was no treatment and no cure.

Desperate, Charlie contacted specialists around the world. “I must have spoken to at least fifty people – scientists, doctors, professors,” he says. “Most of them had never heard of the condition.”

His search eventually led to Dr Wendy Gold, a specialist in rare genetic disorders in children, based at the University of Sydney and the Children’s Hospital at Westmead. “We arranged to talk,” says Charlie. “To be honest, I wasn’t expecting much. But then she said, ‘Have you heard of gene therapy?’”

Gene therapy is a new and rapidly evolving field of research. One of the therapy’s forms involves adding new genes to a patient’s cells to replace missing or malfunctioning genes. The new genes are typically delivered to the appropriate cells in the body using a benign virus as a carrier. Gene therapy is already being used to treat diseases including spinal muscular atrophy. It could also be a promising treatment for Parkinson’s disease. Dr Gold believed there was a chance it could help the Taouk girls.

Finding funding for research into rare medical conditions is a challenge. Pharmaceutical industry funding and other research grants tend to focus on conditions that affect larger numbers of people. Philanthropic support was the only option.

With help from their family, Charlie and Mira have donated $315,000 to fund research to develop the world’s first gene therapy for the PGAP1 mutation. Dr Gold will co-direct the project with Dr Leszek Lisowski, a gene therapy expert at the University of Sydney and the Children’s Medical Research Institute.



The donation from the Taouk family will fund two years of research. The University has launched a crowdfunding campaign to support the project beyond this period.

Within two years, Drs Gold and Lisowski hope to develop a PGAP1 gene addition ready for testing, initially in cells outside the body. It will take longer to investigate the feasibility of a therapy for use inside the human body, so the crowdfunded support is crucial.

Success is not guaranteed, but the team hopes to develop a treatment that will help children around the world. “This is experimental work, so we can’t be sure what will happen, but the goal is a therapy that could be used on other patients with the same mutation,” says Dr Gold. “I’m hoping it will help these girls and other children as well.”

It doesn’t end there. “The tools and knowledge developed during this project will also benefit paediatric patients affected by other genetic disorders,” says Dr Lisowski. “This technology is already curing genetic disorders and changing lives. We are working hard to ensure the gene-therapy revolution benefits Australian paediatric patients as soon as possible.”

Hope, for Charlie and Mira, feels like a risk. But if there’s a chance for their girls, no matter how small, they will take it. “We wake up for them every morning,” says Charlie. “This research – if it works – won’t just be treating two girls. It will be saving a family of four. This is a cure for us, too.”

To contribute to the crowd-funding campaign visit: https://crowdfunding.sydney.edu.au/project/17825