A team of researchers has achieved a significant milestone by developing and delivering a personalized gene-editing therapy to treat an infant diagnosed with carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare genetic disorder. Supported by the National Institutes of Health (NIH), this effort marks the first successful use of such technology in treating a human patient.
The infant, treated at the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania, responded positively to the therapy. The treatment process took six months from diagnosis to administration. Using CRISPR, an advanced gene-editing platform, researchers corrected a specific mutation in the baby's liver cells responsible for CPS1 deficiency. This case represents the first known instance where personalized CRISPR-based medicine was administered to a single patient.
Joni L. Rutter, Ph.D., director of NIH’s National Center for Advancing Translational Sciences (NCATS), stated: “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.”
CPS1 deficiency impairs protein metabolism in the liver leading to toxic ammonia levels that can cause severe brain and liver damage. Standard treatment involves maintaining a low protein diet until a liver transplant is possible; however, during this period there is risk due to potential organ failure from stressors like infection or dehydration.
Rebecca Ahrens-Nicklas, M.D., Ph.D., CHOP pediatrician explained: “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.” After initial low-dose therapy at six months followed by higher doses later on, improvements were observed including increased protein intake and reduced medication needs.
Penn geneticist Kiran Musunuru, M.D., Ph.D., commented on challenges faced during treatment: “We were very concerned when the baby got sick but the baby just shrugged off,” referring to illnesses that would typically be dangerous under such conditions.
This research was presented at the American Society of Gene & Cell Therapy Meeting on May 15th and detailed in The New England Journal of Medicine. Funding came from various NIH grants along with contributions from Acuitas Therapeutics, Integrated DNA Technologies, Aldevron, Danaher Corporation, and CHOP Research Institute’s Gene Therapy Program.
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