Last August, KJ Maldoon was born with a potentially fatal hereditary disorder. Just six months later, he received a CRISPR treatment designed exclusively for him.
Maldoon has a rare disorder known as CPS1 deficiency, where dangerous amounts of ammonia accumulate in the blood. About half of babies born will die early in life. Current treatment options (very restrictive diet and liver transplants) are not ideal. However, the team at Philadelphia Children’s Hospital and Pennsylvania Medicine were able to bypass the standard yearly drug development timeline in a few months and create personalized medicine for KJ.
“We’ve had patients who have faced extremely devastating consequences,” says Kiran Musnoor, a professor of translational research at the University of Pennsylvania and Children’s Hospital of Philadelphia.
When KJ was born, his muscles were stiff, he was lethargic and he didn’t eat. After three doses of his custom treatment, KJ is beginning to hit a developmental milestone that his parents never thought they would see him reach. He can now eat certain foods and stand upright on his own. “He’s made a really big breakthrough,” says his father, Kyle Muldoon.
The case was detailed today in a study published in the New England Journal of Medicine and was presented at the American Gene Cell Therapy Annual Meeting in New Orleans. It can provide a blueprint for performing customized gene editing treatments for other patients with rare diseases who have little or no medical treatment.
When the body digests proteins, ammonia is produced in the process. An important enzyme called CPS1 helps clear this toxic byproduct, but people with CPS1 deficiency lack this enzyme. Too much ammonia in the system can lead to organ damage, and even brain damage and death.
Since KJ’s birth, he has been on a special ammonia-reducing medicine and a low protein diet. However, after administering Bespoke CRISPR medication, KJ was able to take lower medications and start eating more protein without any serious side effects. He is still in the hospital, but his doctors hope to send him home next month or so.
Both KJ’s parents and his medical team stop calling CRISPR therapy a treatment, but they say they are committed to seeing his improvements. “It’s still very early, so we need to continue to monitor KJ closely to fully understand the full effectiveness of this treatment,” says Rebecca Affles Niklas, director of gene therapy at the Hereditary Metabolic Disorders Frontier Program at the Children’s Hospital of Children’s, and assistant professor of pediatric medicine at Penn Medicine, who led the efforts at Musan. She believes that CRISPR treatment has resulted in a milder illness in the severe deficiency of KJ, but she may still need to take medication in the future.
Ahrens-Nicklas and Musunuru worked together in 2023 to explore the possibility of creating customized gene editing therapies for individual patients. They decided to focus on urea circulatory disorders, a group of genetic metabolic conditions that affect the body’s ability to process ammonia, including CPS1 deficiency. In many cases, patients require a liver transplant. The procedure is possible for infants, but it is medically complicated. Ahrens-Nicklas and Musunuru saw the opportunity to find another path.
