A research group funded by the National Institutes of Health (NIH) has successfully created and delivered a personalized gene-editing therapy to treat an infant suffering from a life-threatening, previously untreatable genetic disorder. The baby, diagnosed shortly after birth with the rare condition “carbamoyl phosphate synthetase 1 (CPS1) deficiency”, showed a positive response to the therapy. Remarkably, the entire process—from diagnosis to treatment—was completed in just six months. This marks the first successful use of this gene-editing technology in a human patient. The platform used in the study is adaptable and holds promise for developing personalized therapies for a variety of genetic diseases across different parts of the body.
Researchers from the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania (Penn) created a customized therapy using the CRISPR gene-editing platform. They successfully corrected a specific genetic mutation in the infant’s liver cells that caused the disorder. CRISPR is a cutting-edge technology that allows scientists to make precise edits to DNA within living cells. This marks the first known instance of a personalized CRISPR-based treatment given to an individual patient, specifically designed to target only non-reproductive cells so that the genetic changes remain limited to the treated patient.
CPS1 deficiency is a rare condition in which the liver cannot properly break down the byproducts of protein metabolism, leading to a dangerous buildup of ammonia in the body. This toxic accumulation can severely harm the brain and liver. Treatment typically involves a low-protein diet until the child is eligible for a liver transplant. However, during this waiting period, the child remains vulnerable to sudden organ failure triggered by stressors like infections, injuries, or dehydration. Elevated ammonia levels can result in coma, brain swelling, and may lead to death or permanent brain damage.
The child first received a very low dose of the therapy at six months old, followed by a higher dose later on. Signs of the treatment’s effectiveness appeared early, as the baby was able to tolerate more protein in their diet, and doctors were able to reduce the medications used to control ammonia levels. A key indication of the child’s progress came when they experienced a cold and, later, a gastrointestinal illness—situations that would typically pose serious risks for a child with this condition, including dangerously high ammonia levels in the brain.
The researchers presented their findings at the American Society of Gene & Cell Therapy Meeting on May 15 and detailed the study in The New England Journal of Medicine.