Pioneering gene therapy for Hunter syndrome shows clinical success

A UK toddler with a rare genetic condition was the first person to receive a new gene therapy that appears to halt disease progression.

Oliver, now three years old, has Hunter syndrome, an inherited genetic disorder that leads to physical and cognitive decline. A faulty gene leads to reduced production of an important enzyme that breaks down complex sugar molecules. Over time, these build up throughout the body, causing physical pain, cognitive decline and reduced life expectancy, typically 10-20 years.

'For many years, we have performed bone marrow transplants for children with Hunter Syndrome and similar illnesses. However, these are difficult procedures that can only deliver as much enzyme as the donor's blood naturally has,' said Professor Rob Wynn, consultant paediatric haematologist and director of the paediatric bone marrow transplant programme at Manchester University NHS Foundation Trust.

'Gene therapy is not only safer and more effective, but it enables us to use the child's own cells, which cuts out the need to find a donor, and means we can produce more enzyme for the patient,' he explained.

Currently, the only treatment for Hunter Syndrome is an enzyme replacement therapy known as Elaprase, which is costly and needs to be administered regularly. It also does not efficiently reach the brain due to the blood-brain barrier, which means that cognitive decline in patients continues.

The new gene therapy took ten years to develop at the University of Manchester and was manufactured at the Institute of Child Health, University College London. The one-off treatment uses a similar method to Libmeldy – a treatment already used by the NHS to treat early-onset metachromatic leukodystrophy, an otherwise fatal genetic condition (see BioNews 1132).

Stem cells were taken from the patient's blood, then a virus vector was used to include the corrected DNA, allowing the cells to produce the missing enzyme. These cells carrying the functional copy of the gene were then infused back into the patient, where they produce new white blood cells that make the enzyme. To ensure the treatment reaches the brain, the inserted gene is modified to cross the blood-brain barrier more efficiently.

Oliver is one of five boys to receive the treatment, which was approved in 2022 by the UK medicines regulator. He has stopped receiving Elaprase, but the levels of the enzyme are rising in his blood, suggesting that the treatment is working. Oliver has also shown physical and cognitive improvements, and all participants' progress will be monitored to ensure that they continue producing the enzyme. The gene therapy needs to be delivered early in life, which means that early diagnosis is crucial for other children to have the same opportunity.

'The principles of using gene therapy of blood cells to treat patients with this disease can be applied to many other conditions, which offers exciting prospects for patients and healthcare professionals!', said Professor Wynn.

Hunter syndrome was previously the first genetic condition for which an in-body CRISPR-based treatment was trialled (see BioNews 927).