For the first time, Crispr was used to correct the specific genetic sequence of a patient, a child suffering from a rare disease.
A newborn affected by a rare genetic disease has become the first person in the world to receive genical therapy based on Crispr personalizedthat is, designed specifically to correct the specific mutation that causes its disease. Little KJ Muldoon, who is now 10 months old, received three treatment infusions starting from the sixth month of life and has benefited from it, even if it is not healed. His case was described in an article on New England Journal of Medicine (Nejm) and the annual meeting of the American Society of Gene & Cell Therapy in New Orleans.
The difference compared to the past. It is the first time that a person is treated with a treatment with the Crispr specific for one’s genetic sequenceprobably not usable on anyone else. Already a few dozen people have been treated on genical therapies based on Crispr, but normally, these treatments are designed to work on many people affected by the same disease, regardless of what are the underlying mutations that cause it.
For example, the therapy based on Crispr against falciform anemia and beta-talassemia, the first gene therapy with Crispr to have been approved for clinical use, reactivates the production of fetal hemoglobin, instead of correcting the different possible mutations in the adult form of hemoglobin that cause this condition.
Ammonia in the blood. Little KJ inherited from each of the parents a mutation that prevents producing the normal form of an enzymecalled carbamil-phosphate synthetase 1 (CPS1), essential for urea metabolism. This is an organic compound derived from the metabolism of proteins and eliminated thanks to the kidneys and urinary system in the form of urine. The genetic defect causes an accumulation of nitrogen compounds in the body during the decomposition of proteins, including those introduced with diet. Blood is saturated with ammonia, which damages the brain.
A risk that is worth running. The only solution to the child’s illness – the carbamil -phosphate deficit synthetase 1 (CPS1D), which occurs only in a child on a million born – is the liver transplantation. But to find a suitable one you need time, and the complications of the deficit cause the death of about half of the children who suffer from it.
So Rebecca Ahrens-Nicklas, pediatrician at the Children’s Hospital in Philadelphia (Pennsylvania) proposed to the parents of the newborn a different option: to make the child the first human candidate for Experimentation of a technique to customize basic editinga more precise form than Crispr, in order to correct the specific mutations of a single individual.
A race against time. Basic editing allows you to carry out more precise and targeted interventions and to alter the individual letters of the genetic code (i nucleotids) without cutting the double propeller of the DNA. In just six months, the Ahrens-Nicklas team has developed a base editor to correct one of the defective copies of the CPS1 gene in the newborn, it tested its safety on animals and He got the FDA ok To influence it in KJ’s body, inside lipid nanoparticles. These fat spheres transport the messenger RNA with the instructions to perform the subtle correction in the blood.
Important progress. KJ received the initial dose in February 2025 and two others between March and April. After the first infusion he could already take the daily dose of recommended proteins for his agehowever, combined with drugs to keep the ammonia in the blood under control. After the second and third therapy he was able to gradually lower the level of drugs, even if he cannot do without it. The study obtained the approval of only three infusions which, if they have not led to a cure, however, allowed the child to Avoid liver transplantation and to reach some fundamental stages of development.
An accessible future? The authors of the study believe that this is the future of personalized medicine: treatments such as the one received by KJ could open the way to Care against rare genetic diseases against which there are no options. It remains to be understood how “democratic” these therapies can be, taking into account that, even in the most patient’s versions, they are extremely expensive. The effort in terms of time, work and technologies expenses for the little KJ, operated free of charge by all the professionals involved, is not quantifiable.
