When Rylae-Ann Poulin was one year old, she wasn’t crawling and stammering like other children her age. A rare genetic disease prevented her from lifting her head. Her parents took turns keeping her up at night just so she could breathe comfortably and sleep.

Then, months later. doctors administered gene therapy directly to his brain.

Today, the 4-year-old walks, runs, swims, reads and rides a horse.

Rylae-Ann, who lives with her family in Bangkok, was among the first to benefit from a new way of delivering gene therapy – attacking diseases inside the brain – which experts say holds great promise for the treatment of many brain disorders.

His treatment recently became the first brain-delivered gene therapy after it was approved in Europe and the UK for AADC deficiency, a disorder that interferes with how cells in the nervous system communicate. New Jersey drugmaker PTC Therapeutics plans to seek US approval this year.

Meanwhile, about 30 US studies testing brain gene therapy for various disorders are underway, according to the National Institutes of Health. One, led by Dr. Krystof Bankiewicz of Ohio State University, also targets AADC deficiency. Others are testing treatments for diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.


Challenges remain, especially with diseases caused by more than one gene. But scientists say the evidence supporting this approach is mounting, opening a new frontier in the fight against disorders affecting our most complex and mysterious organ.

“There are a lot of exciting times ahead of us,” said Bankiewicz, a neurosurgeon. “We are seeing breakthroughs.”

The most dramatic of these breakthroughs involves Rylae-Ann disease, which is caused by mutations in a gene needed for an enzyme that helps make neurotransmitters like dopamine and serotonin, the body’s chemical messengers. The single treatment delivers a functional version of the gene.

Around the age of 3 months, Rylae-Ann started having seizures that her parents thought were convulsions – her eyes would roll back and her muscles would tense. Fluid sometimes entered his lungs after feedings, sending him to the emergency room. Doctors thought she had epilepsy or cerebral palsy.

Around the same time, Wei’s brother sent him a message on Facebook about a child in Taiwan with AADC deficiency. The extremely rare disease affects around 135 children worldwide, many of them in this country. Wei, who was born in Taiwan, and her husband, Richard Poulin III, sought a doctor there who correctly diagnosed Rylae-Ann. They learned that she could qualify for a gene therapy clinical trial in Taiwan.

Although they were nervous about brain surgery, they realized she probably wouldn’t live more than 4 years without it.

Treatment Received by Rylae-Ann

Rylae-Ann received the treatment at 18 months on November 13, 2019 – what her parents dubbed her “rebirth day”. Doctors delivered him in minimally invasive surgery, with a thin tube through a hole in his skull. A harmless virus carried in a working version of the gene.

“It gets introduced into the brain cells, and then the brain cells make the (neurotransmitter) dopamine,” said Stuart Peltz, CEO of PTC Therapeutics.

Company officials said all patients in their clinical trials showed motor and cognitive improvements. Some of them, Peltz said, could eventually stand and walk, and continue to improve over time.

Bankiewicz said the roughly 40 patients in his team’s NIH-funded study also saw significant improvements. Its surgical approach is more complex and delivers the treatment to another part of the brain. It targets relevant circuits in the brain, Bankiewicz said, like planting seeds that cause ivy to sprout and spread.

“It really is amazing work,” said Jill Morris, program director at the National Institute of Neurological Disorders and Stroke, which helped fund the research. “And he saw a lot of consistency between patients.”

One of them is Rian Rodriguez-Pena, 8, who lives with his family near Toronto. Rian received gene therapy in 2019, shortly before his 5th birthday. Two months later, she raised her head for the first time. She quickly started using her hands and reaching for hugs. Seven months after the operation, she sat up on her own.

“When the world was collapsing around us with COVID, we were at home celebrating like it was the biggest party of our lives because Rian was crushing so many milestones that had been impossible for so long,” his mother said. , Shillann Rodriguez-Pena. “It’s a completely different life now.”

Scientists say there are challenges to overcome before this approach becomes mainstream for more common brain diseases.

For example, the timing of processing is an issue. Generally, it is better to be earlier in life because illnesses can cause a cascade of problems over the years. In addition, disorders with more complex causes, such as Alzheimer’s disease, are more difficult to treat with gene therapy.

“When you fix a gene, you know exactly where the target is,” Morris said.

Ryan Gilbert, a biomedical engineer at Rensselaer Polytechnic Institute in New York, said there could also be issues with the gene-carrying virus, which can potentially blindly insert genetic information. Gilbert and other researchers are working on other delivery methods, such as messenger RNA — the technology used in many COVID-19 vaccines — to deliver a genetic payload to the nucleus of cells.

Scientists are also exploring ways to deliver gene therapy to the brain without the dangers of brain surgery. But that requires bypassing the blood-brain barrier, an inherent barrier designed to prevent viruses and other germs that might be circulating in the blood from entering the brain.

A more practical hurdle is cost. The price of gene therapies, borne mainly by insurers and governments, can run into the millions. The unique PTC therapy, called Upstaza, costs more than $3 million in Europe, for example.

But drugmakers say they are determined to make sure people get the treatments they need. And the researchers are confident they can overcome the remaining scientific hurdles to this approach.

“So I would say that gene therapy can be used for many kinds of brain diseases and disorders,” Gilbert said. “In the future, you’ll see more technology doing this kind of stuff.”

The families of Rylae-Ann and Rian said they hope other families struggling with devastating genetic conditions will one day see the transformations they have seen. Both girls continue to improve. Rian plays, eats all kinds of foods, learns to walk and works on language. Rylae-Ann is in kindergarten, started ballet class and reads at kindergarten level.

When her dad comes to pick her up, “she runs up to me…just gives me a hug and says, ‘I love you, Dad. he said. “It feels like a normal day, and that’s all we ever wanted as parents.”

The Associated Press Health and Science Department is supported by the Howard Hughes Medical Institute Science and Education Media Group. The AP is solely responsible for all content.

This article is originally published on news-24.fr