2 hours agoShareSaveFergus WalshMedical editorShareSaveChu familyA three-year-old boy has astounded doctors with his progress after becoming the first person in the world with his devastating disease to receive a ground-breaking gene therapy.Oliver Chu has a rare, inherited condition called Hunter syndrome – or MPSII – which causes progressive damage to the body and brain.In the most severe cases, patients with the disease usually die before the age of 20. The effects are sometimes described as a type of childhood dementia.Due to a faulty gene, before the treatment Oliver was unable to produce an enzyme crucial for keeping cells healthy. In a world first, medical staff in Manchester have tried to halt the disease by altering Oliver’s cells using gene therapy.Prof Simon Jones, who is co-leading the trial tells the BBC: “I’ve been waiting 20 years to see a boy like Ollie doing as well as he is, and it’s just so exciting.”At the centre of this remarkable story is Oliver – the first of five boys around the world to receive the treatment – and the Chu family, from California, who have put their faith in the medical team at Royal Manchester Children’s Hospital.A year after starting the treatment, Oliver now appears to be developing normally.”Every time we talk about it I want to cry because it’s just so amazing,” says his mother Jingru.The BBC has followed Oliver’s story for more than a year – including how scientists in the UK first developed the pioneering gene therapy and how the medical trial they are conducting almost didn’t get off the ground due to lack of funds.Stem cell removal – December 2024We first meet Oliver and his dad Ricky in December 2024 at the clinical research facility at Royal Manchester Children’s Hospital. It’s a big day.Since being diagnosed with Hunter syndrome in April, Oliver’s life – like that of his elder brother, Skyler, who also has the condition – has been dominated by hospital visits.Skyler had shown some late development in speech and coordination, but this had initially been put down to being born during Covid.Ricky tells me his sons’ diagnosis came as a complete shock.”When you find out about Hunter syndrome, the first thing the doctor tells you is ‘Don’t go on the internet and look it up because you’ll find the worst cases and you’ll be very, very disheartened’.””But, like anybody, you look it up and you’re like, ‘Oh my goodness, is this what’s going to happen to both my sons?'”Children are born apparently healthy, but around the age of two they start to show symptoms of the disease. These vary and can include changes to physical features, stiffness of the limbs and short stature. It can cause damage throughout the body, including to the heart, liver, bones and joints and in the most serious cases can lead to severe mental impairment and progressive neurological decline.Hunter syndrome almost always occurs in boys. It’s extremely rare, affecting one in 100,000 male births in the world.Until now, the only medicine available for Hunter syndrome was Elaprase, which costs around £300,000 per patient, per year and can slow the physical effects of the disease. The drug is unable to cross the blood-brain barrier and so does not help with cognitive symptoms.But today, Oliver is being hooked up to a machine and having some of his cells removed – the first crucial step in trying to halt his genetic disorder in this one-off treatment.”His blood is being passed through a fancy machine that is collecting a specific type of cell called stem cells which will be sent to a lab to be modified and then given back to him,” Dr Claire Horgan, consultant paediatric haematologist explains.Oliver’s cells are tweaked Oliver’s cells are carefully packaged and sent to a laboratory at Great Ormond Street Hospital (GOSH) in London.In Hunter syndrome, a genetic error means that cells are missing the instructions for making an enzyme, iduronate-2-sulfatase (IDS), essential for breaking down large sugar molecules which over time accumulate in tissues and organs.Scientists insert the missing IDS gene into a virus, which has its genetic material removed so that it can’t cause disease.A similar method has been used in other gene therapies, such as the treatment for another rare inherited condition, MLD.Dr Karen Buckland, from the Cell and Gene Therapy Service at GOSH, explains: “We use the machinery from the virus to insert a working copy of the faulty gene into each of the stem cells.”When those go back to Oliver, they should repopulate his bone marrow and start to produce new white blood cells and each of these will hopefully start to produce the missing protein [enzyme] in his body.”There still remains the issue of how to get enough of the missing enzyme into the brain.To overcome this, the inserted gene is modified so that the enzyme it produces crosses the blood-brain barrier more efficiently.Infusion day – February 2025We next meet Oliver back at the clinical research facility at Royal Manchester Children’s Hospital.This time he’s with his mum Jingru, while Ricky has st …
