In a medical first, doctors raced to create a bespoke CRISPR gene therapy for a boy born with a deadly genetic disease and delivered it to him a mere six and a half months after birth.
The CRISPR treatment was administered safely, and the infant is now growing well and thriving, his doctors say. They hope that the treatment will make a liver transplant, which is usually required for survival, unnecessary for him.
The boy inherited two mutated genes that prevented him from breaking down the proteins in his food, which leads to a build-up of ammonia that destroys the liver and can cause lifelong neurologic damage.
Researchers at the University of California, Berkeley’s Innovative Genomics Institute (IGI) worked with the boy’s physicians at the Children’s Hospital of Philadelphia (CHOP) to test the safety and efficacy of a CRISPR base-editing therapy that hospital doctors had developed. The tests helped fast-track approval of the new therapy by the U.S. Food and Drug Administration.
The boy, KJ Muldoon, was born in August 2024 and immediately had his DNA sequenced, revealing mutations in both copies of the gene for the enzyme carbamoyl phosphate synthetase 1 (CPS1). The mutations prevented his body from making the liver enzyme, which is essential to break down ammonia to urea, which is then excreted in the urine. CPS1 deficiency is one of a group of metabolic diseases, so-called urea cycle disorders, that CHOP physicians have focused on as potentially curable with CRISPR gene editing.