Child with Hunter Syndrome Doing Well After Experimental Gene Therapy

Rare Daily Staff

Several months after a 3-year-old California boy was treated in the United Kingdom with an experimental stem cell gene therapy for Hunter syndrome, a rare lysosomal storage disorder, the child has fully recovered from the procedure.

The boy, Oliver Chu, was treated in a clinical study at Royal Manchester Children’s Hospital in collaboration with the Manchester Centre for Genomic Medicine at Saint Mary’s Hospital — both part of Manchester University NHS Foundation Trust. The trial is managed and sponsored by the University of Manchester.

Children with Hunter syndrome — a rare, inherited condition also known as mucopolysaccharidosis type II, or MPS II — have an error in a gene that prevents them from producing an important enzyme that breaks down complex sugar molecules. Over time, these sugars build up in organs and tissues, leading to joint stiffness, hearing loss, breathing and heart problems, developmental delays, and cognitive decline resembling childhood dementia.

Hunter syndrome can be life-threatening, with life expectancy typically between 10 and 20 years. Currently, the only approved therapy that can help improve life for children with Hunter syndrome is Elaprase, a weekly enzyme replacement therapy that takes about three hours and must be continued for life. About 50 patients in the United Kingdom receive Elaprase, which costs about $476,000 (£375,000) a year per patient. The drug can reduce mobility and organ problems but cannot address mental decline.

The clinical study at RMCH is investigating a one-time gene therapy that involves removing the child’s stem cells, replacing the faulty gene, and reinjecting the modified cells into the patient. These stem cells can produce high levels of the missing enzyme and also reach the brain.

Chu is the first of five children with Hunter syndrome to participate in this study. The research is jointly funded by the University of Manchester and LifeArc, a self-funded not-for-profit medical research organization. It was developed by researchers at MFT and the University of Manchester in partnership with the University of Edinburgh and Great Ormond Street Hospital, where patients’ cells are modified with the missing gene in specialist laboratories.

“We developed an improved method of stem cell gene therapy that adds a short tag to the missing enzyme, allowing it to cross the blood-brain barrier and increase the amount of enzyme delivered to the brain,” said Brian Bigger, honorary professor at the University of Manchester and academic lead. “This helps break down complex sugars that build up in the brain and aims to prevent the devastating dementia-like decline seen in children with severe Hunter disease. Parents have told us that this symptom is the most important factor in improving quality of life for their families.”

Photo: Clinical trial participant Oliver Chu being treated with experimental stem cell gene therapy