Personalized Gene Therapy Saves Infant With Formerly 'Incurable' Disorder

A baby in Pennsylvania has become the first recipient of an experimental genetic therapy that targets a rare urea cycle disorder. The treatment, which involves customizing the gene editing process specifically for an individual’s “faulty” genes, could prove life-saving for the handful of infants born with the condition each year.
The disorder is known as carbamoyl-phosphate synthetase 1 (CPS1) deficiency. CPS1 is a liver enzyme responsible for processing nitrogen-containing compounds; without it, ammonia forms, builds up in the body, and becomes toxic. Every now and then, inherited genetic mutations impact a person’s ability to produce sufficient CPS1, which means those nitrogen compounds—which form naturally as the body breaks down protein—go unattended. 
Until now, the only treatment available for children born with CPS1 deficiency was a liver transplant. But transplant organs are notoriously hard to come by, and the younger and tinier the child, the riskier the transplant will be. Such was the dilemma for KJ Muldoon, a child born at the Hospital of the University of Pennsylvania last year. Just two days after his birth, doctors noticed that KJ was lethargic and, after a multitude of tests, diagnosed him with severe CPS1 deficiency. 
It just so happened that researchers at the nearby Children’s Hospital of Philadelphia (CHOP) had been toying with a novel treatment for CPS1 deficiency (and a handful of related disorders) for two years prior. As KJ was placed on the liver transplant list, the duo—pediatric geneticist Rebecca Ahrens-Nicklas and gene editor Kiran Musunuru—consulted with his parents about the possibility of trying their gene editing technique. Over the course of a few months, they worked to develop a personalized approach to KJ’s specific genetic mutation, which they tested successfully in mice and monkeys. The Food and Drug Administration (FDA) fast-tracked an approval, and on Feb. 25, 2025, KJ became the first patient in the world to receive the experimental treatment.
The process involved using an IV to deliver a CRISPR gene editor to KJ’s bloodstream. In the liver, the editor made single-letter changes to the mutated gene sequences in KJ’s liver. Then, KJ’s family and medical team waited.
A few days after KJ’s treatment, “the color in his cheeks returned,” and he “could tolerate more protein in his diet without causing a toxic increase in ammonia.” KJ’s doctors slowly decreased his life-supporting medications and administered two follow-up CRISPR treatments in two months. Since then, he’s “become more active, playful and more engaged with both his family and the hospital staff who support him,” CHOP says.
The treatment hasn’t just been a success for KJ and his family—it’s also a major win for Ahrens-Nicklas and Musunuru, who dreamed of creating CRISPR treatments that were customized to an individual’s needs.
“This is the first step towards the use of gene editing therapies to treat a wide variety of rare genetic disorders for which there are currently no definitive medical treatments,” Musunuru told the Associated Press.
© 2001-2025 Ziff Davis, LLC., a Ziff Davis company. All Rights Reserved.
ExtremeTech is a federally registered trademark of Ziff Davis, LLC and may not be used by third parties without explicit permission. The display of third-party trademarks and trade names on this site does not necessarily indicate any affiliation or the endorsement of ExtremeTech. If you click an affiliate link and buy a product or service, we may be paid a fee by that merchant.

source