06 November 2023

A revolutionary gene therapy trial for young children diagnosed with Hunter’s syndrome has been given the go ahead in the UK.

The phase 1/2 clinical trial by University of Manchester researchers is now open to recruitment. Up to five infants, aged between three and 12 months, with the rare lysosomal storage disorder will be treated with autologous hematopoietic stem cell gene therapy.

Professor Brian Bigger, professor of cell and gene therapy at the university, published a paper earlier this month that validates the proof-of-concept outcomes findings in mice. The paper is in the journal Molecular Therapy – Methods and Clinical Development.

The researchers hope the findings of their 24-month, single-arm trial into the condition, which is also known as mucopolysaccharidosis type II (MPS II), will remove the need for weekly enzyme replacement therapy over the child’s lifetime.

The UK Medicines and Healthcare Products Regulatory Agency (MHRA), Research Ethics Committee (REC), and Health Research Authority (HRA) approved the clinical trial application. It will be led by Professor Rob Wynn, consultant paediatric haematologist at Royal Manchester Children’s Hospital, Professor Simon Jones, consultant in paediatric inherited metabolic disease at Saint Mary’s Hospital, and Prof Bigger.

Professor Bigger said: “This is a next generation stem cell gene therapy approach, which allows transit of the IDS enzyme into the brain. The newly inserted IDS gene produces an IDS enzyme that contains a proprietary ApoEII-tagged sequence, which can bind to ApoE-dependent receptors on the blood brain barrier, and move enzyme into the brain more efficiently, thus potentially normalising brain pathology.

“This should speed up delivery of enzyme to the brain, where it is most needed as we can leverage all the enzyme produced by the blood to do this rather than just relying on the engraftment of monocyte cells from the blood into the brain.”

He said the pre-clinical studies they carried out in mice showed the potential to correct disease in the body and normalise brain pathology.

“Mice with Hunter syndrome treated with the HSC gene therapy showed dramatic improvement in their condition, including normalisation of working memory problems, and skeletal features such as the cheekbone dimensions and the width of the humerus and femur bones,” he added.

The trial is the culmination of a more than 15-year effort with Professor Wynn and Professor Jones at Manchester University NHS Foundation Trust to develop HSC gene therapies for neurological lysosomal disorders.


Ellison S, Liao A, Gleitz HFE, Parker H, Booth L, Robinson J, Wood S, Taylor J, Holley R, Bigger BW. (2023) “Sustained long-term disease correction in a murine model of MPSII following stem cell gene therapy.” Mol Ther Methods Clin Dev, doi: 10.1016/j.omtm.2023.101127

Link: https://www.sciencedirect.com/science/article/pii/S2329050123001663

Disclaimer: The news stories shared on this site are used as a way to inform our members and followers of updates and relevant information happening in Haematology. The BSH does not endorse the content of news items from external sources, and is not in a position to verify the findings, accuracy or the source of any studies mentioned. Any medical or drugs information is provided as an information resource only, and is not to be relied on for any diagnostic or treatment purposes.

News service provided by Englemed News.