In a first for modern medicine, doctors in the United States have recently used a custom-made gene editing therapy to treat an infant, the first instance of any such therapy being given to a newborn with a lethal genetic disorder.
Infant KJ Muldoon was diagnosed shortly after birth with CPS1 deficiency(Carbamoyl Phosphate Synthetase 1 deficiency), a rare and fatal genetic disease that disrupts the body's removal of toxic ammonia. With the tailor-made treatment developed in record time, doctors have now given KJ a chance at a healthy life, and very likely paved the way toward future treatment of a wide range of inherited diseases.
Customized treatment developed in just six months
Experts at the Children's Hospital of Philadelphia and the University of Pennsylvania got to work shortly after KJ Muldoon was diagnosed. They completed the design, testing, and production of their custom gene-editing therapy in six months, something that normally takes years.
The treatment, given in several infusions starting in February, used a novel method called base editing. The technique can change individual letters in a DNA sequence, fixing genetic errors by not cutting DNA strands.
Although liver transplantation is occasionally an option, the majority of infants with advanced disease are too small or too weak to undergo surgery in time.
Early results are encouraging.
KJ spent the first few months of his life in the hospital on a strict low-protein diet and medication regimen. Physicians have been able to raise his protein levels and lower his medication since receiving therapy. Although KJ's condition is being closely monitored, early signs show positive outcomes. "While KJ will need to be monitored carefully for the rest of his life, our initial findings are quite promising," said Dr. Rebecca Ahrens-Niklaas, director of the Gene Therapy for Inherited Metabolic Disorders Frontier Program at Children's Hospital of Philadelphia.
A breakthrough was made possible by 'years and years of progress' in gene editing. While KJ is just one patient, we hope he is the first of many to benefit.Dr. Rebecca Ahrens-Niklaas, One of the Team's Lead Physicians
"Now, when I get to hold him, and he's laughing and jumping around, that is...very heartwarming, because I didn't know if that was going to happen, at one point," said his mother, Nicole Muldoon.
A milestone for gene editing
The case was published in the New England Journal of Medicine and presented at the American Society of Gene and Cell Therapy conference in New Orleans. The research has been welcomed by scientists around the globe as a breakthrough for gene medicine. [1]
In a post by Dr. Munish Raizada, MD, FAAP at MedBound Hub, he stated:
"Personally, I find it a new day in the annals of medicine.
Baby KJ Muldoon (born in summers of 2024) recently got a permanent solution for an inborn error of metabolism for which there was no known cure.
Doctors at CHOP fixed the defective gene of baby KJ via CRISPR gene therapy. That is the miracle case of CRISPR personalized treatment. The baby was diagnosed with CPS1 (Carbamoyl Phosphate Synthetase 1 ) deficiency. Doctors gave him 3 injections of the gene therapy and it seems his gene was edited and problem fixed. Doctors are still monitoring him and his serum ammonia levels are stable. CPS1 as we know is an urea cycle disorder -a fascinating topic for me personally.
Just a pinch of genetics: Most of the metabolic disorders are inherited as autosomal recessive (AR) disorders."
Join the discussion at MedBound Hub: Mind Blowing: CRISPR fixed a baby’s inborn error of metabolism
“The promise of gene therapy that we’ve heard about for decades is coming to fruition, and it’s going to utterly transform the way we approach medicine,” said Prof Kiran Musunuru at the University of Pennsylvania.
Spain's Dr. Miguel Ángel Moreno-Mateos, a geneticist at Pablo de Olavide University in Seville, agreed:
“Although this has been a very specific approach, partly motivated by the devastating nature of the disease, it represents a milestone that demonstrates these therapies are now a reality. As the article reports, the patient will be monitored for a long time to ensure his well-being and determine whether additional doses are needed to further improve the symptoms of the disease.”
"This is mind-blowing and we should all be very, very excited. We are at day one of, you know, the future of how we are going to treat different diseases. We may have, potentially, treatments for horrible diseases children may be born with," said Dr. Brian Brown, a bioengineer and immunologist who serves as director of the Icahn Genomics Institute at the Icahn School of Medicine at Mount Sinai in New York City.
Looking ahead: An era of personalized medicine
While doctors stress the importance of long-term follow-up, this breakthrough treatment opens up the potential for individualized gene therapy for countless rare diseases. It's a hopeful sign that for families who get nightmare diagnoses in the future, science might have solutions sooner than ever.
Reference:
Musunuru, Kiran, et al. "Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease." New England Journal of Medicine, May 15, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2504747.
Sample, Ian. "US Doctors Rewrite DNA of Infant with Severe Genetic Disorder in Medical First." The Guardian, May 15, 2025. https://www.theguardian.com/science/2025/may/15/us-doctors-rewrite-dna-of-infant-with-severe-genetic-disorder-in-medical-first.
(Input from various sources)
(Rehash/Muhammad Faisal Arshad/MSM)