A BABY has had his DNA rewritten to treat his a deadly genetic disorder in a world first.
Little KJ Muldoon, now 15 months old, was diagnosed with just days after his birth, as he became lethargic and developed breathing problems.
Tests showed that his blood ammonia levels were very high.
Called CPS1 deficiency, it impaired his liver’s ability to process ammonia, which can build up and cause permanent or death.
If a build-up of ammonia were to be left unchecked, it could the tot at risk of death within days.
“You ‘CPS1 deficiency’ and it’s either fatality rate or liver transplant,”;; the baby’s mum, Nicole, said in a video released by Children’s Hospital of Philadelphia (CHOP), where little KJ was treated.
“We were in shock.”;;
CPS1 deficiency is “one of the most severe and rarest urea-cycle disorders”;;, according a Paper Published in the New England Journal of Medicine, penned by scientists who oversaw KJ’s groundbreaking treatment.
The disease its estimated to affect one in 800,000 to one in 1,300,000 births.
At the time of KJ’s, the only way to treat a CPS1 deficiency was a liver transplant, which is better suited to older children who are healthier than KJ was.
But Nicole said: “He was small, but he was stubborn.
The tot’s dad Kyle added: “He was a fighter from the start.”;;
KJ was placed on dialysis to remove the ammonia from his blood and had been living in the hospital, waiting until he was old enough to receive a .
Instead, when he was just six months old, doctors gave him a first dose of a breakthrough gene editing treatment that essentially rewrote his DNA.
A team of scientists at CHOP and the University of Pennsylvania (Penn) had already been researching how to use to create customised treatments for diseases like CPS1 deficiency.
Kiran Musunuru, a cardiologist, geneticist and gene editor at Penn leading the group said: “We’ve been practising developing similar personalised therapies for about two years now with the idea that someday we might be in a position where we could very rapidly try to figure out how to use gene editing to correct a patient’s broken gene that’s responsible for their disease.”;;
Rebecca Ahrens-Nicklas, a paediatric geneticist and Director of CHOP – who also lead the research – spoke about proposing the treatment to KJ’s parents: “My biggest fear in all of this was giving false hope to a family.
“But we got to a point where we thought there might actually be a clinical team and drug development team that could make a drug for KJ.”;;
After six months of work, the team of scientists created infusion just for KJ to fix the genetic mutation causing his rare disease.
“The drug is really designed only for KJ, so the genetic variants that he has are specific to him. It’s ,”;; Dr Ahrens-Nicklas said.
In February 2025, KJ had a drug injected into his bloodstream which used a technology called .
It earned its creators the Nobel prize for chemistry in 2020 and amounts to using a pair of molecular scissors.
Nicole said: “The way I understood gene editing was like writing a sentence on paper.
“When you misspell a word, you go back in and rewrite it to spell it correctly.
“The gene editing would delete the mutated genes from his DNA and replace them with ones that worked properly.”;;
Once the drug had travelled to the liver, the research team programmed the gene editor, CRISPR, to enter the nucleus of KJ’s cells go to the site of the genetic variant that was causing the disease.
The tot received the lowest possible dose of the therapy to allow his body time to adapt and minimise any risks.
‘Scientific miracle’
Just a few days after treatment, KJ began showing sighs of improvement
He was able tolerate more protein in his diet without causing a toxic increase in ammonia and his doctors were able to slowly decrease his ammonia-lowering medication.
The colour also returned to the tot’s cheeks and he had a growth spurt.
Over the next two months, KJ received two additional infusions of the drug, but in higher doses.
He’s still in CHOP being monitored by doctors and has not suffered any serious side effects of the treatment.
“We’ve been operating in fight-or-flight mode for so long, that now it’s finally starting to look like the light at the end of the tunnel,”;; Nicole said.
“When I look back at the little four-pound peanut he was and now see this big, chunky, thriving baby, I’m so glad we were able to push him to show us what he could do and what he could become.”;;
Plans for a transplant have, for the moment, been scrapped.
Scientists are cautious about declaring success, noting that there are still many unknowns for KJ – but they’re hopeful the personalised gene editing has worked.
They said they need to observe KJ for longer to fully evaluate the benefits of this therapy.
But the results so far are promising for other people with genetic conditions, the medical team said.
“Similar therapies could be developed for hundreds of hepatic inborn errors of metabolism,”;; they wrote in their research paper.
Dr Ahrens-Nicklas said she hoped this achievement will allow the boy to get by with little or no medication some day.
“We hope he is the first of many to benefit from a methodology that can be scaled to fit an individual patient’s needs,”;; she added.
Prof Gemma Marfany, professor of genetics at the University of Barcelona, who wasn’t involved in the research, said: “This is the first case of a fully customised therapy, for a single baby treated in vivo with a base-editing therapy for a very severe ultra-rare disease.
“It is truly a unique case, a successful proof of concept, designed and applied in record time, in which researchers and clinicians have not skipped a single preclinical step.
“It seems to me to be a scientific ‘miracle’ that has made it possible to cure a very rare severe disease, and provides knowledge to treat many other diseases.”;;
