Gene editing cures child of rare disease in world first

Telegraph

15-05-2025

A child with an extremely rare genetic disorder has become the first to be genetically edited for his disease in a breakthrough for people suffering from uncommon conditions.
KJ Muldoon was born with a rare metabolic disease known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, which causes a build-up of ammonia and can result in brain damage and organ failure.
It affects fewer than one in a million people, so there is little incentive for pharmaceutical companies to find a treatment.
But in a medical first, doctors at the Children's Hospital of Philadelphia (CHOP) and Penn Medicine, used the genetic editing tool Crispr to correct the defect in his DNA which causes the condition.
Crispr, which acts like genetic scissors to alter genetic code, is already being used for diseases such as sickle cell disease and beta thalassemia which affect hundreds of thousands of people.
It is hoped the technique could be adapted to treat individuals with rare diseases for whom no medical treatments are available.
'Years and years of progress in gene editing and collaboration between researchers and clinicians made this moment possible, and while KJ is just one patient, we hope he is the first of many to benefit from a methodology that can be scaled to fit an individual patient's needs,' said Dr Rebecca Ahrens-Nicklas, director of the Gene Therapy for Inherited Metabolic Disorders Frontier Programme (GTIMD) at the Children's Hospital of Philadelphia.
'While KJ will need to be monitored carefully for the rest of his life, our initial findings are quite promising.'
The personal treatment was developed in just six months and delivered via fatty nanoparticles injected into the liver to correct a faulty enzyme which causes the overproduction of ammonia.
KJ spent the first months of his life in hospital, living a very restricted diet before receiving the first round of his bespoke therapy in February, when he was around seven months old.
He has since had two more injections and doctors say he is now growing well and thriving and has been able to go home.
Kyle Muldoon, KJ's father, said: 'We've been in the thick of this since KJ was born, and our whole world's been revolving around this little guy and his stay in the hospital.
'We're so excited to be able to finally be together at home so that KJ can be with his siblings, and we can finally take a deep breath.'
Typically, patients with CPS1 deficiency are treated with a liver transplant, but they need to be old enough to handle such a major procedure.
Dr Kiran Musunuru, professor for translational research in Penn's Perelman School of Medicine, said: 'We want each and every patient to have the potential to experience the same results we saw in this first patient, and we hope that other academic investigators will replicate this method for many rare diseases and give many patients a fair shot at living a healthy life.
'The promise of gene therapy that we've heard about for decades is coming to fruition, and it's going to utterly transform the way we approach medicine.'
Commenting on the research, Dr Alena Pance, senior lecturer in genetics at the University of Hertfordshire, said: 'Crispr-based therapy has been used to correct genetic diseases before. The approach in the paper is applicable to this specific form of the disease.
'The approach is applicable to any disease caused by a single nucleotide change, however more often than not, diseases are caused by a variety of variants so perhaps more general strategies could be more effective than very precise ones.'
The research was published in the New England Journal of Medicine.