A gene-replacement therapy that is administered directly to the brain has allowed some children with a rare genetic condition to walk and talk for the first time.
鈥淚t鈥檚 a dream come true,鈥� says Richard Poulin, whose daughter Rylae-Ann received the therapy in November 2019, aged 18 months. Rylae-Ann, who lives in Thailand, went from being unable to say any words, move or even lift her head to 鈥渞unning, jumping, kicking a ball, riding a horse, swimming and speaking in multiple languages鈥�, according to Poulin.
Rylae-Ann was born with AADC deficiency, . It is caused by a faulty variant of a gene called DDC that prevents the brain from making dopamine and serotonin.
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Without these important neurotransmitters, children with AADC deficiency 鈥渄on鈥檛 have head control, they cannot sit up, they cannot walk or talk 鈥� they are bedridden鈥�, says Wuh-Liang Hwu at the National Taiwan University Hospital, who led a clinical trial of the gene therapy, called Upstaza. Many also experience 鈥渙culogyric crises鈥�, where their eyes roll up into their heads. Most die at a young age, he says.
Upstaza was developed by PTC Therapeutics, a pharmaceutical company based in New Jersey. It replaces the faulty DDC gene with a version that functions normally. This version is delivered into brain cells via a virus called adeno-associated virus type 2, modified so it doesn鈥檛 harm.
The聽treatment is infused into a聽part of the brain called the putamen through a small hole that is drilled into the skull.
Since 2010, Hwu and his colleagues have trialled the gene therapy in 30 children with AADC deficiency at the National Taiwan University Hospital. The children ranged from 18 months to 10 years old at the time of treatment, and mostly lived in Taiwan and other South-East Asian countries, where the condition is most prevalent.
Following treatment, the children all improved in their motor and cognitive function, and聽had fewer oculogyric crises, according to clinical trial results聽 in Freiburg, Germany.
鈥淭he ones who got it before 4聽years of age, it鈥檚 quite a dramatic difference,鈥� says Hwu. 鈥淲e say they have been reborn.鈥�
Rylae-Ann sat up just one month after receiving the gene therapy. She is one of seven trial participants who have since learned to walk and one of three who have learned to talk. 鈥淪peech is the most difficult thing for patients to learn because it uses so聽many muscles,鈥� says Hwu.
A common side effect of the gene therapy was dyskinesia, or sudden uncontrolled movements, but this resolved in all cases.
In the past, some early gene therapies caused cancer. Upstaza shouldn鈥檛 stimulate abnormal cell growth because the virus used to deliver the DDC gene variant is non-replicating, as are the brain cells it is delivered to, says Hwu.
The gene therapy was approved by the European Medicines Agency in July. PTC Therapeutics plans to seek approval from the US Food and Drug Administration.
Poulin says the therapy has worked better for Rylae-Ann, now 4, than he and her mother Judy could have ever hoped. 鈥淲e didn鈥檛 know what to expect 鈥� would she be able to lift her head? But now, when I get home, she runs up and gives me a big hug and kiss and says, 鈥楧addy, Daddy, I love you鈥�,鈥夆�� he聽says. 鈥淚t鈥檚 incredible.鈥�
