The prize to the best publication on basic research 2008 at the Faculty of Medicine and Dentistry was given to the paper: Identification of pharmacological chaperones as potential therapeutic agents to treat phenylketonuria1

The research Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in phenylalanine hydroxylase (PAH). PKU is characterized by hyperphenylalaninemia which leads to mental retardation if untreated. Restriction of L-Phe intake by using artificial dietary formulations and early diagnosis through newborn screening tests has led to remarkable success in preventing the major manifestations of the disease, including mental retardation. However, lifetime dietary therapy is expensive as well as a social burden, and research for alternative therapies for PKU is encouraged. PKU research has a tradition in our Department, and Professor Torgeir Flatmark performed pioneer work on PAH and PKU associated mutations. In recent years in our group Biorecognition we have focused on the misfolding/destabilizing effect of PAH mutations as the pathogenetic mechanism in PKU, as well as on the stabilization of the mutant proteins by binding of the natural cofactor and pharmacological chaperones. These studies have further lead to the investigation of novel therapeutic approaches for correction of PKU and now more recently of other genetic misfolding diseases. These diseases are associated to mutant proteins -usually enzymeswhich fail to reach their functional form and therefore cannot perform their biological function.