New investigational gene therapy developed following early stage funding from GOSH Charity shows promise for fatal brain disease

Early results of an investigational new therapy used to treat a two-year old with a rare brain disease has shown promise, with findings presented at an international conference.The team announcing this exciting breakthrough is led by The University of Manchester (UoM) and includes researchers from the UCL Great Ormond Street Institute of Child Health (ICH). Great Ormond Street Hospital Children’s Charity (GOSH Charity) provided early funding for the work as part of its commitment to support pioneering medical research that will lead to kinder treatment and potential cures for children with rare and complex conditions.

The condition, Sanfilippo disease type A, is a rare, inherited disease caused by a genetic mutation, which stops the body from being able to break down complex sugar molecules properly. These molecules build up in cells within the brain and nervous system and have a devastating and progressive impact on a child’s development with most patients sadly dying by early adulthood.

With no effective treatments available for their condition, a two-year-old was treated with the investigational gene therapy at Royal Manchester Children’s Hospital (RMCH), part of Manchester University NHS Foundation Trust (MFT), in 2019, under a ‘specials’ license.

The investigational therapy was developed through a decade-long collaboration led by Professor Bigger at UoM, together with ICH researcher and Great Ormond Street Hospital (GOSH) consultant Professor Adrian Thrasher, and Professors Rob Wynn, Ed Wraith and Dr Simon Jones of MFT. It is now being offered to other eligible patients through a world-first clinical trial at MFT, led by The University of Manchester (UoM) and in collaboration with the ICH gene therapy team. The clinical trial is funded by Orchard Therapeutics, who hold the license and commercial rights to the Sanfilippo disease type A programme.

The investigational gene therapy for the clinical trial will be manufactured in the Zayed Centre for Research into Rare Disease in Children, a new state-of-the-art facility representing a partnership between GOSH, UCL and GOSH Charity.

“Gene therapy is such a promising approach and we want to make sure as many children as possible have the chance to benefit,” says Professor Thrasher. “We’re very lucky at GOSH to have a brand-new facility in the Zayed Centre for Research, where we’ll be able to modify the DNA inside patient cells and prepare gene therapies that can be given back to patients for therapeutic benefit.”

GOSH Charity funding helped provide early stage results that secured the future of the project’s development, as Professor Bigger from the University of Manchester explained: “GOSH Charity’s funding helped us, at an early stage in the project, to prove that the idea had legs. It was undoubtedly pivotal in getting us to where we are today — seeing children with Sanfilippo syndrome get access to what could be a life-saving treatment. It’s fantastic to witness, and the families are so excited to have some hope.”

Professor Bigger continued: “These results are promising and provide some hope for these children whose condition was previously thought to be incurable. The trial is the critical next stage, but it’s true to say we are excited.

“Sanfilippo disease is an appalling disease which causes misery to these children- so the prospect of a treatment is tantalising – especially when it was thought for years that no treatment would be possible.”

How the treatment works and its initial results

At an international conference last week, Professor Brian Bigger of the University of Manchester shared growing evidence of the new investigational therapy’s safety and feasibility, marking a vital step forward in the treatment’s development.

GOSH Charity has been a long-term funder in the area of gene therapy, and continues to invest in the development of new technologies and facilities, as well as supporting research projects that aim to translate success of gene therapy for immune conditions to other areas. Sanfilippo syndrome is caused by a ‘mistake’ in the patient’s DNA that leaves them unable to break down complex sugars in the body. These sugars build up and, over time, severely affect their brain function.

Gene therapy is designed to work by correcting the genetic mistake: replacing a ‘faulty’ section of DNA with a healthy one. Cells are taken from the patient, modified in the lab, then returned to the bloodstream, where it’s hoped they will restore production of an enzyme needed to break down complex sugars. The team will closely monitor patients treated as part of the recently launched clinical trial, to understand whether this enzyme production could ultimately slow or prevent progression of the disease.

While it is too early to say whether the treatment will prevent the course of their disease, preliminary results six months after the two-year-old’s treatment indicate greater than normal levels of the enzyme are present in their blood.

The formal clinical trial aims to treat three to five patients aged under two years and follow each patient over the course of three years. The first patient to join the trial was treated earlier in 2020.

A lasting impact in the area of gene therapy

Over the last twenty years, GOSH’s world-leading research team has pioneered gene therapy for childhood immune conditions. Through collaborations with experts around the UK and the globe, the team are now working hard to improve and adapt the technique for other conditions, like Sanfilippo disease.

The clinical trial is funded by Orchard Therapeutics, who hold the license and commercial rights to the Sanfilippo disease type A programme. The trial is also sponsored by the University of Manchester and the gene therapy product is manufactured at the ICH, using the expertise of Professor Thrasher’s specialist gene therapy laboratories.

The Zayed Centre for Research was made possible thanks to a transformative £60 million gift from Her Highness Sheikha Fatima bint Mubarak, wife of the late Sheikh Zayed bin Sultan Al Nahyan, Founder of the United Arab Emirates, in 2014. It is a partnership between Great Ormond Street Hospital, UCL and Great Ormond Street Hospital Children’s Charity.

The early stages of this work were funded in part by Great Ormond Street Hospital Children’s Charity (GOSH Charity) through their annual national funding round for child health research. The manufacturing work on the study was supported by NIHR Great Ormond Street Hospital Biomedical Research Centre (BRC).

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Great Ormond Street Hospital for Children NHS Trust is the country’s leading centre for treating sick children, with the widest range of specialists under one roof.

With the UCL Great Ormond Street Institute of Child Health, we are the largest centre for paediatric research outside the US and play a key role in training children’s health specialists for the future.

Great Ormond Street Hospital Children’s Charity needs to raise money to support the hospital to give children who need help the most the best chance for life. The charity funds patient and family support programmes, provides the latest medical equipment and supports the essential redevelopment of the hospital. It has also launched a five-year strategy to support research into some of the most serious and complex childhood diseases. Great Ormond Street Hospital Children’s Charity is the largest dedicated funder of paediatric research in the UK and our work is entirely funded through the generosity of supporter donations.

For more information visit www.gosh.org