20.05.2025.
KJ was just 2 days old when a doctor at the Hospital of the University of Pennsylvania (Penn) noticed something was wrong. Though the baby seemed healthy at birth, he’d become unusually lethargic, wasn’t eating and struggled to maintain his temperature.
- KJ was born with a rare metabolic disease known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency.
- In a historic medical breakthrough, KJ has been successfully treated with a customized CRISPR gene editing therapy by a team at Children’s Hospital of Philadelphia (CHOP) and Penn Medicine.
After spending the first several months of his life in the hospital, on a very restrictive diet, KJ received the first dose of his bespoke therapy in February 2025 between six and seven months of age. The treatment was administered safely, and he is now growing well and thriving.
“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 Rebecca Ahrens-Nicklas, MD, PhD, 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 at the University of Pennsylvania.
CRISPR (clustered regularly interspaced short palindromic repeats)-based gene editing can precisely correct disease-causing variants in the human genome. Gene editing tools are incredibly complex and nuanced, and up to this point, researchers have built them to target more common diseases that affect tens or hundreds of thousands of patients, such as the two diseases for which there currently are U.S. Food and Drug Administration-approved therapies, sickle cell disease and beta thalassemia.
However, relatively few diseases benefit from a “one-size-fits-all” gene editing approach since so many disease-causing variants exist. Even as the field advances, many patients with rare genetic diseases – collectively impacting millions of patients worldwide – have been left behind.
“While KJ will need to be monitored carefully for the rest of his life, our initial findings are quite promising,” Ahrens-Nicklas 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,”
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.”
A future for KJ
Typically, patients with CPS1 deficiency, like KJ, are treated with a liver transplant. However, for patients to receive a liver transplant, they need to be medically stable and old enough to handle such a major procedure. During that time, episodes of increased ammonia can put patients at risk for ongoing, lifelong neurologic damage or even prove fatal.
Because of these threats to lifelong health, the researchers knew that finding new ways to treat patients who are too young and small to receive liver transplants would be lifechanging for families whose children faced this disorder.
“We would do anything for our kids, so with KJ, we wanted to figure out how we were going to support him and how we were going to get him to the point where he can do all the things a normal kid should be able to do,”
his mother, Nicole Muldoon, said.
“We thought it was our responsibility to help our child, so when the doctors came to us with their idea, we put our trust in them in the hopes that it could help not just KJ but other families in our position.”
“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,” his father, Kyle Muldoon, said. “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.”
Photo: Kiran Musunru, MD, PhD, MPH, ML, MRA, (left) and Rebecca Ahrens-Nicklas, MD, PhD, (right) led the group of researchers from CHOP and Penn who developed a personalized treatment for baby KJ.
