Gene therapy is the idea that people with specific genetic diseases can be helped by carefully editing their genome to correct problems caused by inherited mutations. Gene therapy has been used in attempts to improve life for people with hemophilia, hereditary blindness, Parkinson's disease, sickle cell anemia and other serious health issues.
Today there's a story about a new type of gene therapy which was just used for the first time on a baby born with a severe genetic disorder called CPS1 deficiency. Here's a medical description of what it means.
Carbamoyl phosphate synthetase 1 deficiency (CPSID) is a rare inherited disorder characterized by complete or partial lack of the carbamoyl phosphate synthetase (CPS) enzyme. This is one of five enzymes that play a role in the breakdown and removal of nitrogen from the body, a process known as the urea cycle. The lack of the CPSI enzyme results in excessive accumulation of nitrogen, in the form of ammonia (hyperammonemia), in the blood. Affected children may experience vomiting, refusal to eat, progressive lethargy, and coma. CPSID is inherited as an autosomal recessive genetic disorder.
It's a pretty rare mutation but the results are often tragic depending on the severity and how quickly the infants get treatment. Babies born with it have a build up of ammonia which makes its way to their brain, causing the brain to swell. The disease frequently results in death within a week of birth but even with treatment survivors can experience severe developmental and mental problems. Those who survive will often need a liver transplant but at that point the damage to the brain is irreversible.
Recently a child named KJ Muldoon was born in a Philadelphia hospital with CPS1 deficiency. Doctors explained the disease and likely outcomes to his parents but in this case a group of medical researchers decided to try something new.
The story of KJ’s bespoke gene-editing treatment began on the evening of Aug. 8, when Dr. Kiran Musunuru, a gene-editing researcher at the University of Pennsylvania got an email from Dr. Rebecca Ahrens-Nicklas at the Children’s Hospital of Philadelphia. A baby had been born, and genetic testing showed he had CPS1 deficiency.
Could he save the baby?
Dr. Musunuru had begun investigating the use of gene editing for fairly common gene mutations.
Developing a gene editor to treat patients is a deliberate process that can take years. But KJ did not have years to wait — perhaps as few as six months before a mounting risk of severe brain damage or death.
“At this point, the clock starts in my mind,” Dr. Musunuru said. “This is real life. This is not hypothetical.”
But in six months they got it done. They created a custom CRISPR gene therapy designed specifically correct KJ's defective genes at the single point where they varied from a functional gene.
Dozens of researchers put all else aside for months.
In Berkeley, Dr. Urnov said, “scientists burned a vat of midnight oil on this the size of San Francisco Bay.” He added that “such speed to producing a clinic-grade CRISPR for a genetic disease has no precedent in our field. Not even close.”
David Liu of Harvard, whose lab invented the gene-editing method used to fix KJ’s mutation, said the speed was “astounding.”
In February, KJ got his first treatment with two more to follow.
In February, KJ got his first IV infusion with the gene editing therapy, delivered through tiny fatty droplets called lipid nanoparticles that are taken up by liver cells.
While the room was abuzz with excitement that day, “he slept through the entire thing,” recalled study author Dr. Rebecca Ahrens-Nicklas, a gene therapy expert at CHOP.
After follow-up doses in March and April, KJ has been able to eat more normally and has recovered well from illnesses like colds, which can strain the body and exacerbate symptoms of CPS1. The 9 ½-month old also takes less medication.
Considering his poor prognosis earlier, “any time we see even the smallest milestone that he’s meeting – like a little wave or rolling over – that’s a big moment for us,” his mother said...
“We’re still very much in the early stages of understanding what this medication may have done for KJ,” Ahrens-Nicklas said. “But every day, he’s showing us signs that he’s growing and thriving.”
No one is saying this is a cure. KJ will have to be monitored for years to see how effective the treatment was, but there are signs that he's improving. He's gone from 7th percentile weight for his age to 40th percentile and as mentioned he hasn't been severely impacted by other infections, which is pretty common for infants with CPS1 deficiency. Just look at this little guy. He's looking plump and happy like a newborn should.
An inspiring scientific story that shows what is on the line in our political debates.
— Richard Hanania (@RichardHanania) May 15, 2025
In a world-first medical breakthrough, a baby named KJ Muldoon recently became the first person ever treated with a completely personalized CRISPR gene-editing therapy crafted just for him.… pic.twitter.com/SyTDuFmScv
As a father myself, I'm happy for KJ's parents and I'm glad to see work research this making progress into the real world. There are lots of rare and not-so-rare genetic diseases in the world and I'm looking forward to the day when we can significantly improve life for kids who were dealt a bad hand of cards, gentically speaking. That day is getting closer and with some help from AI, who knows what we'll be able to do a decade from now.
