New hope for children with devastating rare genetic disorder, thanks to world-first research in Manchester

The parents of a three-year-old boy born with a devastating, life-limiting genetic condition say they are now excited for his future after he received a revolutionary stem cell gene therapy treatment developed by researchers in Manchester.

In February this year, Oliver (Ollie) Chu, was treated for Hunter syndrome in a clinical study being delivered at Royal Manchester Children’s Hospital (RMCH) in collaboration with the Manchester Centre for Genomic Medicine at Saint Mary’s Hospital – both part of Manchester University NHS Foundation Trust (MFT). 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 (MPS II), have an error in a gene, meaning they cannot produce 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. Hunter syndrome can be life-threatening, with life expectancy typically between 10 and 20 years. Currently the only licensed drug that can help to improve life for children with Hunter syndrome is Elaprase – a weekly enzyme replacement therapy that takes approximately three hours to administer, that children must take for their whole life. Approximately 50 patients in the UK receive Elaprase, which costs around £375,000 a year per patient. The drug can reduce mobility and organ problems but cannot improve mental decline.

Now, several months on from the procedure, Ollie has fully recovered from the stem cell replacement therapy, and his parents and the Manchester researchers are excited by his progress.

The clinical study at RMCH is investigating a one-off gene therapy which involves removing the child’s stem cells, replacing the faulty gene and re-injecting the modified cells into the patient. These stem cells can produce high levels of the missing enzyme and also reach the brain. Modification of the stem cells takes place in the specialist Cell and Gene Therapy Facility at Great Ormond Street Hospital.

Professor Rob Wynn, Consultant Paediatric Haematologist and Director of Paediatric Bone Marrow Transplant Programme at RMCH and joint study lead, said: “For many years we have performed bone marrow transplant 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.

“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.

“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. Our medicine is becoming safer, and better, and that can only be a good thing!”

Professor Simon Jones Consultant in Paediatric Inherited Metabolic Disease at the Manchester Centre for Genomic Medicine at Saint Mary’s Hospital,  joint study lead, said: “Since having the gene therapy Ollie is no longer having weekly Elaprase infusions, but instead of seeing levels of the previously missing enzyme dropping we are seeing very high levels in his blood, and this is an extremely encouraging sign that the treatment is working.”

Professor Jones is also Medical Director at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at RMCH, which has a key role in the long term follow up of children on this trial and extensive experience in early phase trials in children with complex and rare conditions. He added: “I have worked in researching treatments for children with rare genetic diseases for over twenty years and I have sadly seen many children lose their lives to these devastating conditions. This is a truly exciting development which could lead the way for treating similar genetic conditions and bring hope to other families.”

Ollie Chu is the first of five young 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 organisation. The stem cell therapy was developed by researchers at MFT and The University of Manchester, working in partnership with the University of Edinburgh, Great Ormond Street Hospital (GOSH), and University College London.

Ollie’s story

Ollie was diagnosed with Hunter Syndrome after five-year-old brother, Skyler, was found to have the condition.

Ollie, who lives in California with mum Jingru, dad Ricky, and Skyler travelled to the UK to be part of the research, after tests showed he was still in the early stages of the condition.

Ricky said: “Although it was a big commitment to travel to the UK, of course we want the best for our children, so when this opportunity came up in Manchester, we discussed it as a family. Due to Skyler’s age, he was not eligible to take part in the Manchester trial and is taking part in a different study in the United States. That has meant splitting up the family, but it was something we were willing to do for Ollie to have the opportunity to be in this trial.

“There are very few times where your child can have a reset on life so if you can give them that chance, then it’s just something you do.

“Ollie is doing great since having the gene therapy. We have seen dramatic improvements, and he continues to grow physically and cognitively. Our hope for Ollie because of this treatment is that he will continue to make his own enzymes and live a normal life without infusions.

“We’re excited for Ollie’s future. Seeing the difference for Ollie pre-and post-transplant has made us believers.

“We will be forever grateful to the entire research team for allowing us to be part of this research. I’ve been a huge advocate of this trial.

“We think it’s wonderful that there is research being done on rare conditions. Our priority is our children but knowing that this could result in helping other children around the world is very meaningful for us. We hope that one day, a treatment becomes available for all children at all stages of Hunter syndrome.”

Professor Brian Bigger, Honorary Professor at The University of Manchester, Professor of Advanced Therapeutics at the University of Edinburgh and academic lead said: “This therapy was developed over the course of 10 years at The University of Manchester and seeing this now tested in patients by the clinical team at MFT has been incredibly rewarding.

“We developed an improved method of stem cell gene therapy which adds a short tag to the missing enzyme, allowing it to cross the blood-brain-barrier and improve the amount of enzyme delivered to the brain. 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 to improve quality of life for their family.”

Sam Barrell, Chief Executive Officer, LifeArc, said: “A huge challenge for the more than 3.5 million people in the UK living with rare diseases is getting access to effective treatments – currently 95 per cent of conditions have none – this needs to change. Developing innovative treatments like this are one part of the solution but we crucially need to transform how we support rare disease research and development more broadly in the UK. We must act today to demand better, to work together and change the future for the millions of people living with rare diseases.”

Modification of Ollie’s stem cells took place at GOSH. Dr Karen Buckland, Lead Scientist for Great Ormond Street Hospital’s Cell and Gene Therapy Service and Senior Research Fellow at University College London said: “We are so pleased to hear Ollie is doing well and his family are pleased with the gene therapy. For over 20 years, GOSH has developed a robust method for inserting genes into patients’ stem cells and are pleased to be able to work alongside the teams in Manchester to provide the gene modified cell product for all five patients with Hunter syndrome, and for patients with many other rare diseases using our manufacturing facility at The Zayed Centre for Research into Rare Diseases in Children at GOSH.”

Bob Stevens, Group Chief Executive of the MPS Society, said: “This ground-breaking trial initiated by The University of Manchester has now entered a promising phase, with five children having received gene therapy treatment, starting with Ollie Chu earlier this year who is making good progress. Gene therapy, which uses the patient’s own cells, is showing encouraging signs of improvement as part of the ongoing trial. Seeing this treatment delivered after a decade of development is incredibly rewarding. We remain cautiously optimistic and hopeful that science will continue to offer the chance of a ‘Rare Life Lived Better’.”