LONDON — Researchers at University College London and Great Ormond Street Hospital administered a gene therapy to mice modeling ARC syndrome. The study results were published in the journal Nature Communications.

The therapy involved injecting a functional copy of the VPS33B gene into the mice. The final iteration of the therapy was designed to target liver cells specifically, and none of the mice receiving this formulation developed tumors. Initial versions of the gene therapy had caused liver tumors in approximately 30 percent of the mice. Systemic administration of the treatment yielded better survival outcomes than liver-specific administration.

Approximately 80 percent of the treated mice survived, while approximately 33 percent of untreated mice survived. Treated mice exhibited reduced liver fibrosis. The condition is a genetic disorder typically caused by a deficiency of the VPS33B protein. Children with the condition rarely survive past their first year, and the disorder impairs bile flow from the liver, which can result in fatal sepsis.

"Our findings are important because it provides proof-of-concept that gene therapy could become a realistic treatment for ARC syndrome and potentially other inherited liver diseases that currently have few or no effective options. It also highlights that how a gene therapy is designed is critical: targeting treatment specifically to the liver improved safety while maintaining benefit. Before human trials, further long-term toxicology and safety studies will be needed," said Dr Claudiu Cozmescu, lead author and a researcher at the UCL Great Ormond Street Institute of Child Health.

"The final version of the treatment is shown to be safe so far. The earlier version gave us a new window into the understanding of how to make gene therapies safer for the patients. One of these insights is to keep the levels of genes as close to those found in healthy cells as possible," said Paul Gissen, co-author and Clinical Professor of Paediatric Metabolic Medicine at the institute. GOSH Charity and LifeArc funded the study.

"ARC syndrome is a serious, ultra-rare condition with very limited treatment options. These early findings are an important step towards understanding whether gene therapy could one day offer a new approach for affected children and their families," said George Orphanides, Chief Scientific Officer at LifeArc. Up to six pregnancies per year in the U.K. are estimated to be affected by the syndrome. Researchers used mice genetically engineered to lack functional VPS33B genes.