Progress toward cell‐directed therapy for phenylketonuria

Phenylketonuria (PKU) is one of the most common inborn errors of metabolism with an annual incidence of approximately 1:16,000 live births in North America. Contemporary therapy relies upon lifelong dietary protein restriction and supplementation with phenylalanine‐free medical foods. This therapy is expensive and unpalatable; dietary compliance is difficult to maintain throughout life. Non‐adherence to the diet is associated with learning disabilities, adult‐onset neurodegenerative disease, and maternal PKU syndrome. The fervent dream of many individuals with PKU is a more permanent cure for this disease. This paper will review ongoing efforts to develop viable cell‐directed therapies, in particular cell transplantation and gene therapy, for the treatment of PKU.