Doctors are cautiously optimistic about a groundbreaking gene therapy for children affected by a devastating inherited disorder after seeing positive results in the first boy to receive the treatment.
Three-year-old Oliver Chu from California became the first patient to have the therapy nine months ago as part of a clinical trial run by researchers in Manchester. It is too early to call the therapy a success, but doctors are encouraged by his progress so far.
“Things look really hopeful right now, but Ollie was the first human to receive this therapy and it’s only been nine months out,” said Prof Simon Jones, consultant in paediatric inherited metabolic disease at the Manchester Centre for Genomic Medicine (MCGM) at Saint Mary’s hospital.
“We have four more boys scheduled in and we will need to prove the benefit is long-lasting,” said Jones, the joint leader of the trial.
Oliver was born with a condition called Hunter syndrome. It is caused by a faulty gene that prevents the body from making a crucial enzyme that breaks down complex sugar molecules. Over time, these molecules accumulate in organs and tissues, causing an array of symptoms from joint stiffness and hearing loss to heart problems and cognitive decline, resembling dementia. Life expectancy is typically 10 to 20 years.
The only licensed drug for children with Hunter syndrome is Elaprase, a weekly infusion that replaces the missing enzyme. The treatment costs about £375,000 per patient and must be taken for life. While the drug can improve movement and organ problems, it does not reach the brain and so cannot prevent cognitive decline.
During the one-off therapy in February, doctors collected stem cells from Oliver’s blood and replaced the faulty gene with a working copy. The corrected stem cells were then re-infused back into his bloodstream. There, they began churning out high levels of the enzyme, which also reached his brain.
Since having the therapy, Oliver no longer needs weekly Elaprase infusions, an encouraging sign that the treatment is working. The trial is run from Royal Manchester children’s hospital in collaboration with MCGM at Saint Mary’s.
Speaking to the BBC, Oliver’s father, Ricky, said: “I don’t want to jinx it, but I feel like it’s gone very, very well.
“His life is no longer dominated by needles and hospital visits. His speech, agility and cognitive development have all got dramatically better,” he added. “It’s not just a slow, gradual curve as he gets older, it has shot up exponentially since the transplant.”
Oliver’s parents hope the therapy might also help his elder brother, Skyler, who has the same condition. The therapy cannot reverse existing organ and tissue damage, but tests on Skyler show that despite being five years old, he remains largely unaffected.
Hunter syndrome overwhelmingly affects boys, but is extremely rare, affecting one in 100,000 males born globally. The five boys on the trial are from the US, Europe and Australia. None are from the UK because patients are not diagnosed with the condition soon enough.
“To get the majority of patients treated with this dose we would need newborn screening on the heel prick test, which is now standard for Hunter syndrome in the US,” Jones said. The same gene therapy approach is now being developed to treat other genetic disorders that impair vital enzymes, such as Hurler syndrome and Sanfilippo syndrome.
