Oral administration of phenylalanine molecularly imprinted polymer (MIP) benefits PKU mouse model

Abstract

Phenylketonuria (PKU) is a rare genetic disorder caused by a defect in the metabolism of phenylalanine (Phe). Currently, the most commonly used treatment for PKU is dietary Phe restriction. Problems associated with Phe restricted diets include lack of universal availability, high treatment costs, and reduced adherence to continued treatment with age and finally the development of psychological and neurological problems in a significant proportion of patients despite early start of treatment. One possible approach to decreasing blood Phe level, is inhibition of GI tract absorption of this amino acid. We had previously shown that a Phe selective molecularly imprinted polymer was able to bind Phe in the GI tract and attenuate its plasma concentration. In this work, we used different orally administered Phe selective molecularly imprinted polymer doses in a PKU mouse model to further study the effects of this treatment on biochemical profile and cognitive function in test animals. Treatments started 21 days postnatally. After 3 weeks, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Behavioral profile was also evaluated. Treatment with 2% and 5% Phe selective molecularly imprinted polymer significantly reduced levels of blood Phe in PKU model animals (46% and 48% respectively) meanwhile levels of other amino acids remained unchanged. Brain dopamine concentrations in hippocampus was effectively restored by supplementation of Phe selective molecularly imprinted polymer. Finally, polymer treatment improved locomotor dysfunction in PKU model animals. Our data suggest that the Phe selective molecularly imprinted polymer can be a new candidate for treatment of PKU patients. Take home message: Orally administered Phenylalanine Selective Molecularly Imprinted Polymer is able to inhibit absorption of phenylalanine from the GI tract and may offer a new treatment, in conjunction with dietary restriction, for PKU patients.