The University of Manchester in the UK has partnered with US-based biotech AVROBIO on the clinical development of an investigational gene therapy for mucopolysaccharidosis type II (MPS II), or Hunter syndrome.
Under the terms of the partnership, the University will sponsor the investigator-led phase I/II trial for Hunter syndrome which is expected to begin in 2021.
The Hunter syndrome programme was developed by Brian Bigger, a professor of cell and gene therapy at the University of Manchester. Bigger has already published preclinical data demonstrating that the introduction of the transgene with an optimised, proprietary tag has the ability to correct peripheral disease and normalise brain pathology.
Hunter syndrome causes complications throughout the body and brain, including severe cardiac and respiratory dysfunction, skeletal malformations and hearing impairment.
The current standard-of-care is weekly enzyme replacement therapy, which can delay certain complications but does not stop the overall progression of the disease and does not address cognitive issues.
The investigational gene therapy, AVR-RD-05, involves ex vivo transduction of a patient’s own hematopoietic stem cells with a therapeutic transgene designed to express the functional enzyme that the patient needs to maintain cellular health.
This is coupled with a proprietary protein tag that is designed to improve stability of the enzyme in the bloodstream and aid uptake by tissues throughout the body.
When this is reinfused into the body, the gene-modified stem cells are expected to engraft in the bone marrow and produce generations of daughter cells, each carrying the transgene. These then circulate throughout the body and central nervous system, potentially enabling widespread distribution of the functional enzyme.
“We feel an enormous urgency to bring forward a treatment that may halt this deadly disease in its tracks, before symptoms emerge and before children lose their physical and cognitive skills,” said Professor Bigger.
“We are delighted to be working with AVROBIO on this program. Both of our teams have deep experience running international clinical trials in other lysosomal disorders. AVROBIO also has a leading gene therapy platform, plato, which is designed to optimise the consistency, predictability and efficacy of its gene therapies and to enable efficient scaling for worldwide commercialisation,” he added.