Last August, KJ Muldoon was born with a potentially fatal genetic disorder. Six months later, he received a Crispr treatment specifically designed for him.
KJ has a rare condition called CPS1 deficiency, which leads to a dangerous buildup of ammonia in the blood. Approximately half of infants with this disorder face early mortality. Current treatments—such as a restrictive diet and liver transplantation—are not ideal. A team at the Children’s Hospital of Philadelphia and Penn Medicine, however, managed to bypass the lengthy drug development process and create a personalized Crispr therapy for KJ in a matter of months.
Professor Kiran Musunuru, from the University of Pennsylvania and Children’s Hospital of Philadelphia, who was part of the team, stated, “We had a patient who was facing a very, very devastating outcome.”
Upon his birth, KJ exhibited rigid muscles, lethargy, and refused to eat. After three doses of the customized treatment, KJ began reaching developmental milestones previously thought unattainable. He can now consume certain foods and sit upright independently. His father, Kyle Muldoon, remarked on KJ’s “tremendous strides.”
Details of the case are featured in a study published in The New England Journal of Medicine and were presented at the American Society of Gene & Cell Therapy annual meeting in New Orleans. This case may serve as a blueprint for developing customized gene-editing treatments for other rare diseases with limited treatment options.
When protein is digested, ammonia is produced. The enzyme CPS1 helps eliminate this toxic byproduct, but individuals with CPS1 deficiency lack this enzyme. Excessive ammonia can lead to organ damage, brain damage, and potentially death.
Since birth, KJ has been on ammonia-reducing medication and a low-protein diet. However, after receiving the specialized Crispr drug, KJ has been able to reduce his medication dosage and increase protein intake without experiencing serious side effects. He remains in the hospital, but doctors hope he will be discharged soon.
Both KJ’s parents and his medical team cautiously view the Crispr therapy as promising, acknowledging improvements. Rebecca Ahrens-Nicklas, director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at Children’s Hospital of Philadelphia and assistant professor of pediatrics at Penn Medicine, cautioned that continued monitoring is necessary to fully understand the therapy’s effects. She noted that while the treatment likely transformed KJ’s severe deficiency into a milder form, future medication may still be required.
Ahrens-Nicklas and Musunuru collaborated in 2023 to assess the potential of creating personalized gene-editing therapies. They chose to focus on urea cycle disorders, a group of genetic metabolic conditions affecting ammonia processing, including CPS1 deficiency. Patients often need a liver transplant, a complex procedure, especially in infants. Ahrens-Nicklas and Musunuru aimed to explore alternative solutions.
