Alternative therapies to address the unmet medical needs of patients with phenylketonuria

• Verfasst von: Blau, Nenad [VerfasserIn]
• Verfasst von: Longo, Nicola [VerfasserIn]
• Titel: Alternative therapies to address the unmet medical needs of patients with phenylketonuria
• Verf.angabe: Nenad Blau, Nicola Longo
• Umfang: 10 S.
• Fussnoten: Gesehen am 14.08.2017
• Titel Quelle: Enthalten in: Expert opinion on pharmacotherapy
• Jahr Quelle: 2015
• Band/Heft Quelle: 16(2015), 6, S. 791-800
• ISSN Quelle: 1744-7666
• DOI: doi:10.1517/14656566.2015.1013030
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1562416618

Abstract

Standard therapy for phenylketonuria (PKU), the most common inherited disorder in amino acid metabolism, is an onerous phenylalanine-restricted diet. Adherence to this stringent diet regimen decreases as patients get older, and this lack of adherence is directly associated with cognitive and executive dysfunction and psychiatric issues. These factors emphasize the need for alternative pharmacological therapies to help treat patients with PKU. Sapropterin dihydrochloride is a synthetic form of tetrahydrobiopterin, the cofactor of phenylalanine hydroxylase that in pharmacological doses can stabilize and increase residual enzyme activity in some patients with PKU. About one-third of all patients with PKU respond to oral sapropterin. Phenylalanine ammonia lyase (PAL) is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. Phase I and II trials have shown that injectable recombinant Anabaena variabilis PAL produced in Escherichia coli conjugated with PEG can reduce phenylalanine levels in subjects with PKU. The most frequently reported adverse events were injection-site reactions, dizziness and immune reactions. Additionally, oral administration of PAL and delivery of enzyme substitution therapies by encapsulation in erythrocytes are being investigated. Novel therapies for patients with PKU appear to be options to reduce phenylalanine levels, and may reduce the deleterious effects of this disorder.