New UK collaboration provides hope of gene therapy for liver condition

Professor Ian Alexander CMRI
Professor Ian Alexander CMRI

A new collaboration between Children’s Medical Research Institute (CMRI) and Bloomsbury Genetic Therapies Limited (Bloomsbury), a clinical-stage biotechnology company based in the UK, could see a novel gene therapy for a devastating genetic liver metabolic condition enter clinical trials within months – providing hope for children who currently have to undergo liver transplantation to survive.

The collaboration, which involves research teams from CMRI’s Translational Vectorology Unit, the Gene Therapy Research Unit, a joint initiative of CMRI and Sydney Children’s Hospitals Network, and Bloomsbury, was born out of an academic collaboration between CMRI and University College London and Great Ormond Street Hospital in London to develop curative treatments for patients.

Professor Ian Alexander heads the Gene Therapy Research Unit. Several years ago he began a collaboration with clinician-scientists and experts in paediatric metabolic disease, Professor Paul Gissen and Dr Julien Baruteau in the UK, to develop gene therapies for infants and children suffering from a group of rare metabolic liver diseases known as urea cycle defects.

Their first project, working with Dr Sharon Cunningham and Associate Professor Leszek Lisowski at CMRI, involved developing a gene therapy for the most common urea cycle defect, ornithine transcarbamylase deficiency (OTC deficiency). In this disorder, the liver is unable to perform the normal processes of converting highly toxic ammonia, produced by protein breakdown, into relatively harmless urea which can be cleared from the body in urine. In untreated patients with OTC deficiency, ammonia can accumulate in the body to toxic levels causing severe brain damage and even death.

Teresa Hanna is pictured with son Emmanuel who has OTC deficiency
Teresa Hanna is pictured with son Emmanuel who has OTC deficiency

Professor Alexander, who is also a paediatrician at The Children’s Hospital at Westmead, said the research program had received critical early funding from the Medical Research Council in the UK, and was subsequently licensed to Bloomsbury to continue its development, and the resultant gene therapy is likely to reach clinical trials within a matter of months.

“This is an exciting opportunity because current medical treatments are inadequate, leaving liver transplantation as the only potentially curative option’’ Professor Alexander said. “High unmet need makes OTC deficiency an ideal early target in the development of gene therapies for metabolic liver diseases affecting children. If this is successful, we hope to bring this new therapy to Australia and also want to look at applying the same gene transfer approach  to other conditions.’’

”The extensive research on the optimization and characterization of gene therapies for liver disorders initiated over a decade ago by Professor Ian Alexander, Dr Sharon Cunningham and Associate Professor Leszek Lisowski and their teams has resulted in the design of a best-in-class gene therapy treatment candidate for OTC deficiency, and we are looking forward to supporting our collaborators from University College London as they initiate the HORACE trial (Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn; NCT 05092685) very soon”, said Adrien Lemoine, Chief Executive Officer and co-founder of Bloomsbury.

Sydney mother Teresa Hanna’s fifth child Emmanuel was born with OTC deficiency. He almost died just 48 hours after birth and suffered brain injury from the condition. He had a liver transplant before his first birthday and the family donated his liver to the Gene Therapy Research Unit for research. Now aged five, he is a happy boy attending school, but he cannot walk or talk. Teresa was delighted when informed about the trial.

“I am thrilled to hear about the gene therapy trial. If Emmanuel would have had the opportunity to benefit from gene therapy, he would not have needed a liver transplant or to live being immunosuppressed and on continuous medication for the rest of his life. This is a giant leap forward in research.’’

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