Mucopolysaccharidosis II, known as MPS II or Hunter Syndrome, is a progressive and life-threatening rare condition that occurs primarily in males, affecting around 1 in 150,000 newborns. This inherited lysosomal disease is characterised by distinctive facial features, a large head, dementia in childhood, enlargement of the liver and spleen (hepatosplenomegaly), umbilical or inguinal hernia, and hearing loss. Whilst the condition can be managed through enzyme replacement therapies, there is currently no cure.
Manchester Clinical Research Facility (MCRF), Manchester University NHS Foundation Trust (MFT) and the University of Manchester (UoM) have created a strategic partnership with AvroBio – a Massachusetts-based biotechnology company focused on delivering step-change cell and gene therapies targeting cancer and rare disease – to trial a first-in-person ex vivo gene therapy treatment using lentiviral vector-modified stem cells at the MCRF at Royal Manchester Children’s Hospital (RMCH) – part of MFT
The revolutionary gene therapy technology follows over a decade of development and pre-clinical work by Professor Brain Bigger at UoM, working with clinical collaborators including Dr Simon Jones, Director of the MCRF at RMCH. It was licensed to AvroBio in late 2020.
This one-off treatment, designed to address all aspects of the disease, will transplant a manufactured gene-modified stem cell product back into the patient. The stem cells then regenerate the immune system providing the patient with the working copy of the gene.
RMCH’s Bone Marrow Transplant (BMT) Unit, led by Professor Rob Wynn, has pioneered transplants for children with similar metabolic diseases and enzyme deficiencies for many years, and is the largest transplant centre for metabolic diseases in Europe.
The trial will recruit between five and 10 participants, all aged under two years old, from across the globe, with both recruitment to the trial and treatment expected to begin before the end of 2022. Treatment will last for approximately three months, with participants followed-up for an initial two-to-three-year period. If successful, the aim is for the treatment to be rolled out across the NHS, and the rest of the world, as standard clinical practice.
As part of the strategic partnership, the MCRF clinical team will continue to work with the AvroBio team on a series of further research programmes; collaborating on trial protocols and enabling more rapid set-up of Phase 1 and 2 trials across MCRF, sponsored by UoM.
As a result of the cutting-edge genetic research conducted at the MCRF at RMCH, and its ability to deliver complex, high-intensity studies and treatments, through dedicated world-class facilities and highly-trained and experienced staff, a recent European Medicines Agency approved gene therapy for the treatment of metachromatic leukodystrophy (MLD) will be delivered at MFT – one of only five sites across Europe.