A new therapy prevents intellectual disability in mouse with phenylketonuria

Tiziana Pascucci, Luigia Rossi, Marco Colamartino, Claudia Gabucci, Claudia Carducci, Alessandro Valzania, Valeria Sasso, Noemi Bigini, Francesca Pierigè, Maria Teresa Viscomi, Rossella Ventura, Simona Cabib, Mauro Magnani, Stefano Puglisi-Allegra, Vincenzo Leuzzi

Research output: Contribution to journalArticlepeer-review


Untreated phenylketonuria (PKU) results in severe neurodevelopmental disorders, which can be partially prevented by an early and rigorous limitation of phenylalanine (Phe) intake. Enzyme substitution therapy with recombinant Anabaena variabilis Phe Ammonia Lyase (rAvPAL) proved to be effective in reducing blood Phe levels in preclinical and clinical studies of adults with PKU. Aims of present study were: a) to gather proofs of clinical efficacy of rAvPAL treatment in preventing neurological impairment in an early treated murine model of PKU; b) to test the advantages of an alternative delivering system for rAvPAL such as autologous erythrocytes. BTBR-Pahenu2-/- mice were treated from 15 to 64 post-natal days with weekly infusions of erythrocytes loaded with rAvPAL. Behavioral, neurochemical, and brain histological markers denoting untreated PKU were examined in early treated adult mice in comparison with untreated and wild type animals. rAvPAL therapy normalized blood and brain Phe; prevented cognitive developmental failure, brain depletion of serotonin, dendritic spine abnormalities, and myelin basic protein reduction. No adverse events or inactivating immune reaction were observed. In conclusion present study testifies the clinical efficacy of rAvPAL treatment in a preclinical model of PKU and the advantages of erythrocytes as carrier of the enzyme in term of frequency of the administrations and prevention of immunological reactions.

Original languageEnglish
Pages (from-to)39-49
Number of pages11
JournalMolecular Genetics and Metabolism
Issue number1
Publication statusPublished - May 2018


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