May 20, 2025 – A landmark study from the Children’s Hospital of Philadelphia (CHOP) and Penn Medicine has showcased the power of a customised gene editing therapy to treat a patient with a rare metabolic disease.
A child diagnosed with rare genetic disorder severe carbamoyl phosphate synthetase 1 (CPS1) deficiency was successfully treated with a customised CRISPR gene editing therapy.
The case is detailed in a study published by The New England Journal of Medicine and was presented at the American Society of Gene & Cell Therapy Annual Meeting in New Orleans.
The landmark finding could provide a pathway for gene editing technology to be successfully 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,” commented Rebecca Ahrens-Nicklas, Director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program (GTIMD) at Children’s Hospital of Philadelphia and an Assistant Professor of Pediatrics in the Perelman School of Medicine.
Realising the promise of gene therapy
Ahrens-Nicklas and Kiran Musunuru, the Barry J Gertz Professor for Translational Research at Penn Medicine, began collaborating to study the feasibility of creating customiaed gene editing therapies for individual patients in 2023, building upon many years of research into rare metabolic disorders, as well as the feasibility of gene editing to treat patients.
Both are members of the NIH-funded Somatic Cell Genome Editing Consortium, which supports collaborative genome editing research.
Ahrens-Nicklas and Musunuru decided to focus on urea cycle disorders. A child with a urea cycle disorder lacks an enzyme in the liver needed to convert ammonia to urea. Ammonia then builds up to a toxic level, which can cause organ damage, particularly in the brain and the liver.
Ahrens-Nicklas and Musunuru targeted KJ’s specific variant of CPS1, identified soon after his birth. Within six months, their team designed and manufactured a base editing therapy delivered via lipid nanoparticles to the liver to correct KJ’s faulty enzyme.
Acuitas Therapeutics provided a lipid nanoparticle (LNP) delivery vehicle that was clinically vetted and safe to administer to a newborn baby.
As of April, KJ had received three doses of the therapy with no serious side effects. In the short time since treatment, he has tolerated increased dietary protein and needed less nitrogen scavenger medication.
He also has been able to recover from certain typical childhood illnesses like rhinovirus without ammonia building up in his body. However, longer follow-up is needed to fully evaluate the benefits of the therapy.
Musunuru said: “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.”
Diana Spencer, Senior Digital Content Editor, DDW
Image: Penn Medicine’s Kiran Musunuru and Rebecca Ahrens-Nicklas holding KJ post infusion. © Children’s Hospital of Philadelphia
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