Pennsylvania Baby Thrives After Receiving First Personalized Gene Therapy

A Pennsylvania infant born with a rare and life-threatening genetic disorder is now thriving thanks to an experimental gene-editing therapy tailored specifically for him.

Researchers published details of the case in the New England Journal of Medicine, highlighting it as one of the first instances where a personalized gene therapy successfully corrected a tiny yet deadly genetic mutation. The achievement offers hope for millions suffering from ultra-rare conditions who have been left behind by recent advances in genetic medicine.

“This marks the beginning of using gene editing to treat a broader range of rare genetic diseases that currently lack definitive treatments,” said Dr. Kiran Musunuru, a gene-editing specialist from the University of Pennsylvania and a co-author of the study.

The baby, KJ Muldoon from Clifton Heights, PA, joins the 350 million people worldwide who live with rare diseases — most of them genetic. Diagnosed shortly after birth with CPS1 deficiency, a condition affecting roughly one in a million babies, KJ lacked a crucial enzyme for removing ammonia from the blood. Without it, toxic buildup can lead to death. A liver transplant is sometimes used as a last resort.

Parents Kyle and Nicole Muldoon, both 34, were thrust into uncertainty. “We were weighing every option,” Nicole recalled, comparing the risks of a liver transplant to the untested therapy. Her husband added, “We prayed, asked questions, and ultimately felt this was our path.”

In a matter of months, researchers from Children’s Hospital of Philadelphia and Penn Medicine developed a therapy to repair KJ’s genetic error using CRISPR, the gene-editing tool that earned a Nobel Prize in 2020. Instead of cutting DNA, this therapy used base editing — a method that flips a single incorrect base in the DNA sequence — minimizing unintended genetic alterations.

“This rapid development is remarkable,” said Dr. Senthil Bhoopalan of St. Jude Children’s Research Hospital, who was not part of the study. “It’s a new benchmark for personalized gene therapies.”

In February, KJ received his first IV infusion of the treatment, delivered via lipid nanoparticles targeting liver cells. “He slept through the entire procedure,” said Dr. Rebecca Ahrens-Nicklas, a gene therapy expert at CHOP and one of the authors of the study.

He continued with follow-up infusions in March and April. Since then, KJ has shown significant improvement. He can eat more normally and bounce back from illnesses — such as the common cold — that would typically exacerbate CPS1 symptoms. He also relies less on medication.

Given his grim prognosis early on, each small milestone is cause for celebration. “A wave, a roll-over — these feel monumental to us,” said his mother.

Still, researchers are cautious. They stress that it’s only been a few months since the therapy began. “We’re still trying to understand the full impact of this treatment,” Ahrens-Nicklas noted. “But every day, KJ gives us signs he’s doing better.”

The hope is that KJ’s case will blaze a trail for treating other rare disorders. Historically, gene therapies target more common conditions for financial reasons — more patients mean a better return on the enormous cost of development. The first CRISPR-based treatment approved by the FDA was for sickle cell disease, which affects millions.

But Musunuru emphasized that customized therapies don’t have to be financially out of reach. His team’s work, partly funded by the NIH, cost roughly the same as a liver transplant — around $800,000 — including related medical care.

“As we refine our techniques and speed up the development process, economies of scale will lower these costs,” he explained.

Bhoopalan added that future custom therapies will benefit from the groundwork laid here, eliminating the need to start from scratch every time. “This paves the way for addressing more rare conditions.”

Dr. Carlos Moraes, a neurology professor at the University of Miami uninvolved in the study, said breakthroughs like KJ’s have a ripple effect. “Once one team proves it’s possible, others follow. Barriers will fall within five to ten years, and the whole field will evolve together.”