Groundbreaking Personalized Gene Therapy Saves Infant with Rare, Incurable Disease

In a historic leap for personalized medicine, a research team supported by the National Institutes of Health (NIH) has successfully developed and administered a customized gene-editing therapy to treat an infant with carbamoyl phosphate synthetase 1 (CPS1) deficiency—a rare and life-threatening genetic disorder.

This is the first known instance of a CRISPR-based therapy being tailored for and delivered to an individual patient. The achievement marks a promising new direction in the treatment of rare genetic diseases.

From Diagnosis to Treatment in Just Six Months
Diagnosed shortly after birth, the infant suffered from CPS1 deficiency, a metabolic disorder that disrupts the body’s ability to eliminate ammonia—a toxic byproduct of protein metabolism. If left untreated, it can lead to severe brain damage, organ failure, or death within days of birth.

Thanks to the rapid deployment of a customized gene therapy developed by researchers at the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania, the infant received treatment just six months after diagnosis.

“As a platform, gene editing—built on reusable components and rapid customization—promises a new era of precision medicine for hundreds of rare diseases, bringing life-changing therapies to patients when timing matters most: early, fast, and tailored to the individual,” said Joni L. Rutter, Ph.D., director of NIH’s National Center for Advancing Translational Sciences (NCATS).

A Tailored CRISPR-Based Approach
The treatment used CRISPR, an advanced gene-editing technology known for its precision. The research team corrected the child’s specific genetic mutation in liver cells—targeting only somatic (non-reproductive) cells to ensure the changes affect only the patient.

CHOP pediatrician Rebecca Ahrens-Nicklas, M.D., Ph.D., explained their cautious but strategic approach: “We knew the method used to deliver the gene-editing machinery to the baby’s liver cells allowed us to give the treatment repeatedly. That meant we could start with a low dose that we were sure was safe.”

The child initially received a very low dose, followed by a higher one. Encouraging signs of recovery emerged quickly. The infant could tolerate a higher protein intake, required fewer medications to control ammonia levels, and, significantly, responded resiliently to common illnesses like a cold and a gastrointestinal bug—events that might otherwise have proven fatal.

“We were very concerned when the baby got sick, but the baby just shrugged the illness off,” said Kiran Musunuru, M.D., Ph.D., Penn geneticist and first author of the study.

Hope for the Future of Rare Disease Treatment
The team’s findings were presented at the American Society of Gene & Cell Therapy Meeting on May 15th and published in The New England Journal of Medicine.

While further monitoring and research are essential, this breakthrough suggests that customized gene-editing therapies could become viable treatment options for other patients with rare genetic disorders. It also showcases the power of cross-institutional collaboration, involving NIH support and contributions from industry leaders like Acuitas Therapeutics and Integrated DNA Technologies.

This remarkable case not only offers new hope to families affected by devastating genetic diseases but also sets the stage for the rapid development of similar therapies using the same flexible, patient-specific approach.

Source – NIH