Journal of Inherited Metabolic Disease

, Volume 29, Issue 6, pp 732–738

Large neutral amino acids in the treatment of phenylketonuria (PKU)

  • R. Matalon
  • K. Michals-Matalon
  • G. Bhatia
  • E. Grechanina
  • P. Novikov
  • J. D. McDonald
  • J. Grady
  • S. K. Tyring
  • F. Guttler
Original Article

DOI: 10.1007/s10545-006-0395-8

Cite this article as:
Matalon, R., Michals-Matalon, K., Bhatia, G. et al. J Inherit Metab Dis (2006) 29: 732. doi:10.1007/s10545-006-0395-8

Summary

Large neutral amino acids (LNAAs) 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 earlier studies on mice with PKU (ENU2/ENU2), LNAAs were given and a surprising decline in blood Phe concentrations was observed. The formula used in the mouse experiment (PreKUnil) lacked lysine. Therefore, a new formulation of LNAAs (NeoPhe) was developed, introducing changes in the concentration of some amino acids and adding lysine, so that such a mixture could be used in humans. The new formula was found to be effective in reducing blood Phe concentration in mice by about 50% of the elevated levels. Patients with PKU were given LNAAs and blood Phe concentrations were determined in an open-label study. Three centres—in Russia, the Ukraine and the USA—took part in the study. NeoPhe was given at 0.5 g/kg per day in three divided doses to eight subjects with PKU and at 1.0 g/kg per day to three patients, for one week. The NeoPhe resulted in decrease of elevated blood Phe by 50% in both groups. The preliminary data from this study are encouraging and a double blind placebo-controlled trial will be required to show long-term efficacy and tolerance of LNAAs in the treatment of PKU.

Abbreviations

CSF

cerebrospinal fluid

5-HIAA

5-hydroxyindolacetic acid

LNAA

large neutral amino acid

Phe

phenylalanine

PKU

phenylketonuria

VIL

valine, isoleucine and leucine

Copyright information

© SSIEM and Springer 2006

Authors and Affiliations

  • R. Matalon
    • 1
  • K. Michals-Matalon
    • 2
  • G. Bhatia
    • 1
  • E. Grechanina
    • 3
  • P. Novikov
    • 4
  • J. D. McDonald
    • 5
  • J. Grady
    • 1
  • S. K. Tyring
    • 6
  • F. Guttler
    • 7
  1. 1.Department of PediatricsUniversity of Texas Medical Branch, Children‘s HospitalGalvestonUSA
  2. 2.University of HoustonHoustonUSA
  3. 3.Institute of Clinical GeneticsKharkiv State Medical UniversityKharkivUkraine
  4. 4.Department of Clinical GeneticsInstitute of Pediatrics and Child SurgeryMoscowRussia
  5. 5.Wichita State UniversityWichitaUSA
  6. 6.University of Texas-Health Science CenterHoustonUSA
  7. 7.Kennedy InstituteGlostrupDenmark