Hunter syndrome (or MPS II) is a rare genetic condition that causes progressive damage to the brain and other parts of the body. In the most severe cases, patients usually do not live beyond the age of 20, and the effects of the syndrome are compared to a form of childhood dementia.
Before treatment, Cho was unable to produce an enzyme necessary for healthy cells due to a defective gene.
But medical teams in Manchester (UK) tried to stop the progression of the disease by modifying Cho cells through gene therapy.
Professor Simon Jones, who co-led the study, told the BBC: ‘I’ve waited 20 years to see a boy like Zhou progress so well, which is very exciting.’
At the heart of this story is Cho, the first of five boys in the world to receive treatment, and his family in California, who put their trust in the medical team at Manchester Royal Children’s Hospital.
One year after starting treatment, Cho appears to be progressing normally.
“Every time we talk about it, I want to cry because it’s unbelievable,” says Mum Jingro.
The BBC has been following Oliver Chu’s journey for more than a year, including the development of a pioneering gene therapy by scientists in the UK and the financial challenges that almost prevented the start of a clinical trial.
Stem Cell Removal – December 2024
We meet Oliver Chu and his father Ricky in December 2024, at the Clinical Research Center at Manchester Royal Children’s Hospital. It was an important day.
Since being diagnosed with Hunter syndrome, in April of that year, Cho’s routine – as well as that of his older brother Skyler, who suffers from the same condition – has been limited to frequent visits to the hospital.
Skylar suffered from speech and coordination delays, initially linked to the fact that he was born during the COVID pandemic.
Ricky says his sons’ diagnosis came as a shock.
“When you discover Hunter syndrome, your doctor immediately warns you: ‘Don’t look on the Internet, because you will find the worst cases and you will feel very frustrated.’
“But like everyone else, you look for it and think: ‘Oh my God, is this what’s going to happen to my baby?’
The babies were born apparently healthy, but began showing signs of illness around the age of two.
Symptoms vary and may include changes in physical features, stiffness of the extremities, and short stature.
Hunter syndrome can affect the entire body, including the heart, liver, bones and joints, and in more severe cases, causes severe mental impairment and progressive neurological deterioration.
Hunter syndrome almost always occurs in boys. It is extremely rare: it affects one in every 100,000 male births worldwide.
Until now, the only drug available was Elaprase, which costs around £300,000 (about R$2.1 million) per patient per year and helps slow the physical effects of the disease. The drug does not cross the blood-brain barrier and therefore does not affect cognitive symptoms.
But that day, Cho was hooked up to a machine to remove some of his own cells, the first step in trying to stop his genetic disorder through this unique treatment.
“His blood passes through a sophisticated machine that collects a specific type of cell, a stem cell, which will be sent to the laboratory to be modified and then returned to him,” explains pediatric hematologist Claire Horgan.
Oliver Chu’s cells were modified
Cho’s cells are carefully packed and sent to the laboratory at Great Ormond Street Hospital in London.
In Hunter syndrome, a genetic defect means that cells don’t have the instructions to produce the enzyme iduronate-2-sulfatase (IDS), which is necessary to break down large sugar molecules that build up over time in tissues and organs.
Scientists insert the missing IDS gene into a virus that has had its genetic material removed so it won’t cause disease.
A similar approach has already been used in other gene therapies, such as in the treatment of another rare genetic condition, metachromatic leukodystrophy (MLD).
Karen Buckland, from the Cell and Gene Therapy Service at Great Ormond Street Hospital, explains: “We use the virus construct to insert a working copy of the defective gene into each of the stem cells.
“When they get back to Cho, they should repopulate his bone marrow and start producing new white blood cells, all of them hopefully producing the protein (enzyme) his body is missing.”
The challenge still remains: getting the enzyme to the brain in sufficient quantities.
To solve this problem, the introduced gene is modified so that the enzyme produced can cross the blood-brain barrier more efficiently.
Leak day – February 2025
We meet Cho again at the Clinical Research Center at Manchester Royal Children’s Hospital.
This time he was with his mother, Jingro. Ricky stayed in California to care for Skyler. There is an air of anticipation as a member of the research team opens a large metal cryopreservation tank in which Zhou’s genetically modified stem cells brought back from Great Ormond Street Hospital are frozen.
A small, clear infusion bag is extracted and heated slowly, until it reaches body temperature, in a tray of liquid.
After several checks, the nurse transfers the liquid, which contains about 125 million modified stem cells, into a syringe.
Oliver Chu is used to going to hospitals, but he fidgets as the nurse injects the treatment, the equivalent of a full cup, into the catheter installed in his chest.
Jinju holds him tightly in her arms. After ten minutes, the infusion ends.
An hour later, a second identical infusion is applied. Cho continues to watch the graphics on a portable screen, oblivious to the possible impact of what just happened.
And that’s it. Gene therapy completed. The procedure seems quick, but the ambition is enormous: halting the progressive progression of Cho’s disease with a single treatment.
A few days later, Zhou and Jingru return to California. Now the family and medical team have to wait to see if the treatment is successful.
Early signs of progress – May 2025
In May, Zhou returns to Manchester to conduct crucial tests that indicate the success of the gene therapy. This time the whole family accompanies him.
We met in a downtown park, and it became immediately clear that there was reason for optimism.
Chu is more active and curious than I’ve ever seen him before. It is true that he is now free to play and has been released from hospital, but he looks more prepared and healthier.
Ricky can’t hide his joy: “He’s doing great. We’ve seen improvements in his speech and mobility. In just three months, he’s matured.”
The big news is that Cho was able to stop the weekly injections of the enzyme he was missing.
“I want to pinch myself every time I tell people that Cho produces its own enzyme,” Gengro says. “When we talk about it, it makes me want to cry, because it’s amazing.”
She says he is “completely different” than he was before treatment, talking “a lot more” and interacting more with other children.
It is also a pleasure to meet five-year-old Skylar, who is affectionate and protective of her younger brother.
“My request from the star is that Skylar receive the same treatment,” Ricky says. “It looks like Cho got a fresh start in life, and I want that for Skyler too, even though he’s a little older.”
Initially, it was thought that Zhou was already outside the age range of the clinical trial, because the treatment did not reverse the damage that had already occurred. But tests showed he was still barely affected.
Skyler shows joy in the world around her and soon wants to hold my hand and talk as we walk to the park.
Ricky explains that his son has delayed development of speech and motor skills, but is undergoing infusion therapy, which delivers the treatment to the body rather than the brain.
“Forever grateful”
Oliver Chu returns to Manchester every three months for follow-up checks for a few days.
At the end of August, new analyzes confirm that gene therapy is effective.
Zhou is showing vitality, and has so far completed nine months since treatment.
Professor Jones, whom Cho calls Santa Claus because of his white beard, is thrilled. “Before the transplant, Ollie (Cho) was not producing any enzymes. Now, he is producing hundreds of times the normal amount. Most importantly, we see that he is improving, learning, acquiring new words and skills, and moving more easily.”
However, Jones remains cautious. “We have to be careful and not get carried away by excitement, but things are as good as can be at this stage.”
On the hospital rooftop garden, Cho plays with his father.
“He looks like a completely different kid,” Ricky says. “He’s running all over the place, and he won’t stop talking.”
“Chou’s future looks very bright, and we hope this will allow more children to receive treatment.”
In total, five boys are participating in the clinical trial, coming from the USA, Europe and Australia. None of them were from the UK, because British patients were diagnosed too late to qualify.
All participants will be monitored for at least two years. If the trial is successful, the hospital and university intend to partner with another biotech company to license the treatment.
The same approach is being applied to other genetic disorders, Jones says. Similar treatments are being trialled in Manchester for MPS type 1, or Hurler syndrome, and MPS type 3, or Sanfilippo syndrome.
Ricky and Jingro say they are “forever grateful” to the Manchester team for allowing Cho to take part in the shoot. They say they are impressed with the progress their son has made in recent months.
Oliver is now producing the missing enzyme, and his body and brain are healthy.
“I don’t want to celebrate too early, but I feel like it went really well,” Ricky says.
“His life is no longer dominated by needles and hospital visits. His speech, agility and cognitive development have improved dramatically.
“It’s not just a slow, gradual curve as it grows, it’s a curve that has gone up dramatically since the transplant.”
The rehearsal that almost didn’t happen
Researchers at the University of Manchester, led by Professor Brian Pager, have spent more than 15 years developing gene therapy for Hunter syndrome.
In 2020, the university announced a partnership with the small American biotechnology company Afrobio to conduct a clinical trial.
But three years later, the company returned the license to the university, after unsatisfactory results from another gene therapy study and a lack of resources.
The groundbreaking human experiment that would soon help Oliver Chu was compromised before it even began.
“We had to move quickly to try to save the idea, find another sponsor and another source of funding,” Jones says.
Then the British medical research organization LifeArc stepped in, providing £2.5 million (about R$17.5 million).
Chief executive Sam Burrell said: “The key challenge facing the more than 3.5 million people in the UK with rare diseases is access to effective treatments. Currently, 95% of cases have no cure.”
The Cho family is relieved that the experiment has not been stopped and now hopes that Cho’s brother Skyler will also benefit from the same gene therapy in the future.
“I will walk to the ends of the world, backwards, forwards, upside down, barefoot, to make sure my children have a better future,” Ricky says.
This text was originally published here.
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