GOSH manufactures new gene therapy for rare condition

Three-year-old Ollie Chu received the one-off gene therapy as part of a clinical trial 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).

Children with Hunter syndrome, 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 treatment 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.

The laboratory team at GOSH manufactured the gene therapy for the patients in the specialist Cell and Gene Therapy Manufacturing Facility in The Zayed Centre for Research (ZCR) into Rare Diseases in Children at GOSH.

This is the first ex-vivo (outside of the body) gene therapy to treat the condition.

The process to manufacture the gene therapy first saw white blood cells being removed from the patient in Manchester and then shipped to the ZCR in London.

The white blood cells are then purified to retrieve the stem cells, which are then added to a specialist growth medium. A working copy of the gene is added to a viral vector, which is used to transport the healthy copy of the gene into the patient’s own stem cells.

The cells are then washed and frozen and stored at -130 degrees C, in a process known as cryopreservation. The cells are checked using several quality control tests to make sure they’re safe to be given back to the patient. All the tests were passed and so the cells were approved by a specialist pharmacist, which is called batch certification.

Once the treatment was certificated, it was shipped back to Manchester to be infused into the patient.

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.”

Several months on from the procedure, Ollie has fully recovered from the gene therapy, and his parents and hospital teams are excited by his progress.

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 Rob Wynn, Consultant Paediatric Haematologist and Director of Paediatric Bone Marrow Transplant Programme at Royal Mancher Children’s Hospital 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!”

Ollie Chu is the first of five young children with Hunter syndrome to participate in this study. Two patients have so far been given the gene therapy, and the specialist team is currently making a third.

The Cell and Gene Manufacturing Facility in The Zayed Centre for Research is the UK’s largest academic Good Manufacturing Process (GMP) facility, with seven clean rooms.

The Zayed Centre for Research into Rare Diseases in Children was built thanks to funding from GOSH Charity and was made possible by a £60 million gift in 2014 from Her Highness Sheikha Fatima bint Mubarak, wife of the late Sheikh Zayed bin Sultan Al Nahyan, the founding father of the United Arab Emirates.

The research is jointly funded by The University of Manchester and LifeArc. The stem cell therapy was developed by researchers at MFT and The University of Manchester, working in partnership with the University of Edinburgh, GOSH, and University College London. The trial is managed and sponsored by The University of Manchester.