CRISPR Therapy Saves Infant With Rare Genetic Disorder

Doctors at Children’s Hospital of Philadelphia have reported a breakthrough use of CRISPR gene editing to treat an infant with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare and typically fatal metabolic disorder. The condition, caused by a unique genetic mutation, prevents the liver from processing ammonia, leading to toxic buildup that can damage the brain and other organs.

K.J. Muldoon, born prematurely in Philadelphia, was diagnosed shortly after birth. Without intervention, he would have required a liver transplant. Instead, researchers created a customized CRISPR-based therapy, approved for use within six months, and delivered it directly to his liver via lipid nanoparticles in three doses between February and April.

Doctors Kiran Musunuru and Rebecca Ahrens-Nicklas, shown with K.J. Muldoon after his gene-editing infusion. Photo: Children’s Hospital of Philadelphia / The Wall Street Journal

The therapy targets K.J.’s specific mutation and enables his liver to produce the missing enzyme. While long-term efficacy is still unknown, early signs are promising: K.J.’s ammonia levels are down, his protein intake has increased, and his weight has risen from below the 10th percentile to above the 35th. He now sits up, drinks from a bottle, and is expected to go home soon.

Dr. Kiran Musunuru of Penn Medicine, one of the lead developers, said the case could serve as a model for rapidly developing individualized CRISPR therapies for other patients with rare, patient-specific mutations. Read the full story here.

Topics: Novel Therapeutics