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

Reuben Matalon, K. Michals-Matalon, G. Bhatia, E. Grechanina, P. Novikov, J. D. McDonald, J. Grady, S. K. Tyring, F. Guttler

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)732-738
Number of pages7
JournalJournal of Inherited Metabolic Disease
Volume29
Issue number6
DOIs
StatePublished - Dec 2006

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Neutral Amino Acids
Phenylketonurias
Phenylalanine
Lysine
Therapeutics
Ukraine
Russia
Placebos
Amino Acids
Brain

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Endocrinology

Cite this

Matalon, R., Michals-Matalon, K., Bhatia, G., Grechanina, E., Novikov, P., McDonald, J. D., ... Guttler, F. (2006). Large neutral amino acids in the treatment of phenylketonuria (PKU). Journal of Inherited Metabolic Disease, 29(6), 732-738. https://doi.org/10.1007/s10545-006-0395-8

Large neutral amino acids in the treatment of phenylketonuria (PKU). / Matalon, Reuben; Michals-Matalon, K.; Bhatia, G.; Grechanina, E.; Novikov, P.; McDonald, J. D.; Grady, J.; Tyring, S. K.; Guttler, F.

In: Journal of Inherited Metabolic Disease, Vol. 29, No. 6, 12.2006, p. 732-738.

Research output: Contribution to journalArticle

Matalon, R, Michals-Matalon, K, Bhatia, G, Grechanina, E, Novikov, P, McDonald, JD, Grady, J, Tyring, SK & Guttler, F 2006, 'Large neutral amino acids in the treatment of phenylketonuria (PKU)', Journal of Inherited Metabolic Disease, vol. 29, no. 6, pp. 732-738. https://doi.org/10.1007/s10545-006-0395-8
Matalon, Reuben ; Michals-Matalon, K. ; Bhatia, G. ; Grechanina, E. ; Novikov, P. ; McDonald, J. D. ; Grady, J. ; Tyring, S. K. ; Guttler, F. / Large neutral amino acids in the treatment of phenylketonuria (PKU). In: Journal of Inherited Metabolic Disease. 2006 ; Vol. 29, No. 6. pp. 732-738.
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