A baby with a rare genetic disease has been successfully treated with a personalised CRISPR therapy, in a pioneering breakthrough published in the journal ‘NEJM’.
WORLD’S FIRST CASE
A baby is the first documented case of a baby with a serious genetic disease being successfully treated with a personalised CRISPR gene-editing-based therapy.
A team of researchers from the Children’s Hospital of Philadelphia and the University of Pennsylvania (USA) has achieved this historic breakthrough by adapting the technology and administering it to a single human patient, marking a turning point in the treatment of rare genetic diseases.
KJ, as the baby is called to maintain his anonymity, was diagnosed shortly after birth with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare metabolic disorder that prevents the liver from properly processing ammonia, a toxic substance generated in the breakdown of proteins. This build-up can cause severe brain and liver damage and can even be fatal.
After his diagnosis, and at just six months of age, KJ received the first dose of an experimental therapy specifically designed to correct the mutation that caused his disease. The therapy, developed in record time – just six months from the identification of the genetic defect – uses CRISPR-based gene editing and was delivered to the baby’s liver via lipid nanoparticles.
Since February 2025, KJ has received three doses of this therapy with no serious adverse effects. According to the team, the baby has shown clear signs of improvement: he tolerates a higher protein diet, has reduced his dependence on drugs that remove excess nitrogen, and has overcome common illnesses such as colds and gastrointestinal problems without elevating his ammonia level, which would be extremely dangerous in his condition.
The research, published in The New England Journal of Medicine and presented at the Annual Meeting of the American Society for Gene and Cell Therapy, demonstrates that CRISPR-based precision medicine can be rapidly tailored to individual needs.
This methodology, developed by Dr Rebecca Ahrens-Nicklas and Dr Kiran Musunuru, both experts in genetics and metabolism, can be replicated to treat other rare genetic diseases that, until now, had no therapeutic options.
KJ’s case represents the culmination of years of research and collaboration,’ says Ahrens-Nicklas. Although he is just one patient, we hope he is the first of many who will benefit from this personalised approach.
‘The gene therapy dream we have been pursuing for decades is starting to become a reality. This modular and reusable platform allows us to act quickly and in a targeted way when it matters most: in early childhood, before the disease causes irreversible damage,’ adds Musunuru.
Liver transplantation
Under normal conditions, the standard treatment for CPS1 deficiency is liver transplantation, an intervention that requires the patient to be medically stable and old enough. KJ, like many other babies with this condition, could not wait that long without risking irreversible neurological damage or even death.
‘We knew that if we didn’t do something in time, KJ might not be a candidate for a transplant,’ Ahrens-Nicklas explains. Thanks to this experimental gene therapy, it has been possible to avoid or postpone the need for a transplant, giving the child a chance for normal development.
The success of this intervention opens the door to a new therapeutic model for ultra-rare diseases. This personalised approach could be replicated for hundreds of genetic disorders, providing targeted, safe and rapid treatments where previously there was no hope.
Three experts consulted by SMC highlight the results of this work.
Marc Güell, from Pompeu Fabra University, says that the study ‘reflects the great potential of gene editing for therapeutic purposes’. Fernando Civeira Murillo, from the University of Zaragoza, describes the study as ‘excellent’, with the only limitation being that ‘the follow-up is short’.
Güell considers that it fits perfectly with the current evidence and says: ‘Probably in a few years the vast majority of severe monogenic diseases will disappear thanks to gene editing’.
Finally, Gemma Marfany, from the University of Barcelona and CIBERER, highlights the fact that it is ‘the first case of a totally customised therapy, for a single baby’, and calls it ‘a scientific “miracle” that has made it possible to cure a very rare severe disease’.
Author: Rafael Ibarra
date:15/05/2025
Mofidied 16/05/2025 a las 10:43h.
Source: Abc.es
Note: The Nutrigenomics Institute is not responsible for the opinions expressed in this article.
Photo of Kiran Musunuru y Rebecca Ahrens-Nicklas KJ wiht the paciente at Children’s Hospital of Philadelphia
