Journal of Inherited Metabolic Disease

, Volume 30, Issue 2, pp 153–158

Double blind placebo control trial of large neutral amino acids in treatment of PKU: Effect on blood phenylalanine

Authors

    • Department of PediatricsUniversity of Texas Medical Branch, Children’s Hospital
  • K. Michals-Matalon
    • University of Houston
  • G. Bhatia
    • Department of PediatricsUniversity of Texas Medical Branch, Children’s Hospital
  • A. B. Burlina
    • Inherited Metabolic Disease Unit and Department of Neuroscience, Neurological ClinicUniversity Hospital of Padua
  • A. P. Burlina
    • Inherited Metabolic Disease Unit and Department of Neuroscience, Neurological ClinicUniversity Hospital of Padua
  • C. Braga
    • Diagnósticos Laboratoriais Especializados and Centro Ambulatorial de Prevenção/APAE-Rio de Janeiro
  • L. Fiori
    • Department of PediatricsSan Paolo Hospital, University of Milan
  • M. Giovannini
    • Department of PediatricsSan Paolo Hospital, University of Milan
  • E. Grechanina
    • Institute of Clinical GeneticsKharkiv State Medical University
  • P. Novikov
    • Department of Clinical GeneticsInstitute of Pediatrics and Child Surgery
  • J. Grady
    • Department of PediatricsUniversity of Texas Medical Branch, Children’s Hospital
  • S. K. Tyring
    • University of Texas-Health Science Centre
  • F. Guttler
    • Kennedy Institute
ICIEM 2006

DOI: 10.1007/s10545-007-0556-4

Cite this article as:
Matalon, R., Michals-Matalon, K., Bhatia, G. et al. J Inherit Metab Dis (2007) 30: 153. doi:10.1007/s10545-007-0556-4

Summary

Large neutral amino acids (LNAA) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In an open-label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short-term double-blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres – Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double-blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment.

Abbreviations

BBB

blood–brain barrier

LNAA

large neutral amino acids

Phe

phenylalanine

PKU

phenylketonuria

VIL

valine, isoleucine and leucine

Copyright information

© SSIEM and Springer 2007