Novel Approaches to the Therapy of Phenylketonuria

Abstract

Since its discovery by Følling in 1934, phenylketonuria (PKU) has been the subject of numerous research studies spanning many disciplines including human genetics, biochemistry, development, neurobiology and others. During the last 75 years, different mutations in the genes responsible for the disease have been mapped, the biochemical basis has been elucidated and the flawed mechanisms leading to the clinical outcome have been revealed. Moreover, the newborn screening programs based on the Guthrie test and the subsequent biochemical analysis in newborn children, in addition to the low-protein diet, have all made a tremendous impact on the way inherited inborn errors of metabolism have been looked upon in these modern times. In fact, this simple yet most effective treatment for PKU – the low-protein diet – is considered a breakthrough in treatment of the disease enabling the retention of low levels of phenylalanine in the blood, thus preventing the high and persistent phenylalanine levels from damaging normal brain development. However, despite the simplicity and high effectiveness of the low-protein diet treatment, the incompliance of some PKU patients and the consequences that are associated with it have led scientists to constantly seek new and alternative methods for treatment. In this review, we discuss major advances in PKU therapy, including suggested new cures. We remain optimistic that one or more of the potential cures reviewed here will evolve into future medications for PKU patients.