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

Autor: J. D. McDonald, Elena Grechanina, Stephen K. Tyring, Reuben Matalon, Kimberlee Michals-Matalon, Flemming Güttler, James J. Grady, Gita Bhatia, P. Novikov
Rok vydání: 2006
Předmět:
Zdroj: Journal of Inherited Metabolic Disease. 29:732-738
ISSN: 1573-2665
0141-8955
DOI: 10.1007/s10545-006-0395-8
Popis: 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 (ENU(2)/ENU(2)), 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 centers--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.
Databáze: OpenAIRE
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