At least a handful of times a year, unpredictable seizures overcome two young Sydney sisters and cut off their airways.
Every moment matters in their parents’ subsequent scramble for an ambulance, because Mary, 14, and Neveah Taouk, 10, are both largely resistant to anti-epileptic drugs.
This is because their seizures are the result of an ultra-rare gene disorder known as PGAP1-CDG.
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The degenerative gene defect — which also causes severe intellectual disability — is only known to be carried by 23 other people in the world.
PGAP1-CDG falls into the “ultra-rare” disorder category, so pharmaceutical companies are generally not interested in developing a treatment and governments do not typically fund them.
This means it almost always falls to the parents to pioneer the hugely expensive research required to develop a treatment.
For PGAP1-CDG, the mammoth task was taken on by Mary and Neveah’s parents, Charlie and Mira Taouk, who have already pumped more than $380,000 into the research but have now hit a financial roadblock.
They have turned to crowd-funding with GoFundMe to try to support continued research.
“If we didn’t do it, nobody was going to do it for us,” Charlie told 7NEWS.com.au.
“I’m not expecting a cure but I’ll take anything, even if it just helps the seizures, just to improve their quality of life.
“One minute she’s her bubbly self, and the next she’s blue in the face and not breathing.
“It just destroys you watching them suffer.”
‘We feel every single one’
More than a decade of watching their daughters experience the brain-damaging seizures has not made it any easier for Charlie and Mira.
Charlie usually takes the lead in their emergency responses, as unbearable panic each time grips Mira.
“She just can’t handle it, and I don’t blame her. It’s just the worst thing to watch. Not knowing how long it’s going to last for,” Charlie said.
“We feel every single one of them.”
Mary was not born with symptoms but after six months she had not met key development milestones.
“She was like a rag doll,” Charlie said. “All her limbs just flopped, she couldn’t even hold her own head up.”
Testing began soon after, but they would not get answers for another seven years.
At the time their paediatrician was convinced Mary had cerebral palsy and told the young parents the chance of having another child with the same birth defect was extremely low.
It was a heartbreaking blow for Charlie and Mira when Neveah also began to show signs of the same condition as her sister months after she was born.
“I can’t describe the feeling we felt after they told us that she most likely had whatever Mary’s got. Back then, they didn’t even know what it was,” Charlie said.
Charlie and Mira also have a one-year-old daughter, Veronica, who does not have the same gene defect — she was conceived through IVF as a precaution and underwent genetic testing “to make sure that didn’t happen”.
Charlie describes Mary and Neveah as “gentle girls”.
“When they’re well, they’ve always got nice, bright smiles.”
The girls are high-needs children — they need help to eat, drink, dress and bathe — so caring for them is a full-time job for Charlie and Mira, who also manage the girls’ continence issues, physiotherapy and cognitive exercises.
At night, the parents sleep beside monitors that measure the girls’ oxygen saturation levels and heart rate, in case of a seizure — the regular false alarms which pull them panicked from their bed are each time better than the heartbreaking alternative.
“As a family, it doesn’t get harder than this,” Charlie said.
“You don’t get more heartache than this, you don’t get more stress and anxiety and worry than this.”
Breakthroughs and barriers
A diagnosis in 2019 was the family’s first breakthrough. As soon as they received it, they reached out to about 50 doctors and scientists around the world.
Charlie said one of those experts told him: “The only hope your children have is gene therapy” — which cannot correct damage already done, but can stop the progression of disease.
For this to work, a virus needs to be created with a correct copy of the mutated gene. That virus, when released within the patient, believes it is infecting a patient’s cells with its own DNA, but it is actually transferring the functional gene.
On paper — and on the petri dish — Mary and Neveah initially appeared to be “a textbook case for gene therapy,” Charlie said.
Within two years, the correct gene-implanted virus was latching onto Mary and Neveah’s cells, and everything looked “brilliant”.
But when it came to testing the virus on specially-bred mice, Charlie said “it was as if we had injected them with water”.
The gene therapy research had hit a devastating roadblock, just as their funding was running dry — but not before Charlie said a “hunch” led to their scientists to a breakthrough.
‘A small molecule, by chance’
Dr Leszek Lisowski is the world-leading vectorology expert spearheading the research for Mary and Neveah — his laboratory, which operates from the Sydney’s Children’s Medical Research Institute (CMRI), specifically focuses on rare genetic disorders.
“Most of the programs we run in my lab were actually initiated by an email or a phone call from a family that got a diagnosis and found there was no treatment,” Lisowski told 7NEWS.com.au.
“We make it part of our mission to never turn anyone away.”
All of Lisowski’s projects are “high-risk” due to unsustainable funding, but it is the close relationships with families that this work involves that keeps him going.
“Charlie very often says this, which really resonates with me, we’re not developing treatment for his daughters, we’re developing treatment for his family,” Lisowski said.
“It is, you know, curing the kids, but it’s really curing the whole family unit, which is extremely heartwarming.”
Lisowski has two of his 20 scientists working on Mary and Neveah’s case — he said it moves slowly now that he funds the project himself, feeling a sense of obligation to continue “now that I have the lead”.
Researchers discovered “a small molecule, by chance,” Charlie said, and it appears on a cellular level to be improving the symptoms of PGAP1-CDG.
“That was a huge breakthrough.”
Lisowski said: “That’s how the second phase of the project — which is not a gene therapy, it’s a small molecule therapy — was initiated. We’ve been pushing that for the last two years and we are now moving toward the clinical phase.”
The oral pill they are making from the molecule will hopefully stop Mary and Neveah’s seizures, and offer a brain reset allowing them to begin learning.
Bbut Lisowski said because the disease has never been treated, “we don’t actually know what’s going to happen”.
‘It takes an army’
A gene defect is “a random event that can happen to anyone” and Lisowski describes having a child as a punt in the “genetic lottery”.
There are about 10,000 known genetic disorders, most of them rare, and every tenth child born has one.
“Globally, that’s eight million children born every year, and two million of them are not living past five, not celebrating their birthday,” Lisowski said.
“We are sort of fighting it together, but separately.”
While many suffer, Lisowski said developing treatments for them is not a “commercially viable model”.
“The financial commitment (pharmaceutical companies) would have to make to actually develop a drug cannot then be recovered from the number of patients. They would have nobody to sell the drug to.”
Governments also need to decide the most helpful places to direct their funding, and Lisowski said “not one” of the 10 rare genetic disease treatments he is researching is supported by government funding.
While Lisowski’s lab “always struggles for funding”, it still manages to achieve lifechanging results. His team recently developed a therapy for a rare disease, and the first patient was treated in December.
“It was really the community that made it possible … it’s a global network of people that has to come together to help an individual, one person, one child,” he said.
“You know, it takes a village to raise a child but it really takes an army to cure one.”
To learn more about the other families turning crowd-funding for PGAP1-CDG research, visit their GoFundMe page.
