Large neutral amino acids in the treatment of phenylketonuria (PKU).
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.
Matalon
R
R
Department of Pediatrics, University of Texas Medical Branch, Childrens Hospital, Galveston, Texas, USA. rmatalon@utmb.edu
Michals-Matalon
K
K
Bhatia
G
G
Grechanina
E
E
Novikov
P
P
McDonald
J D
JD
Grady
J
J
Tyring
S K
SK
Guttler
F
F
D000293:Adolescent; D000328:Adult; D021542:Amino Acids, Neutral / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004032:Diet; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008297:Male; D051379:Mice; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000188:drug therapy*; D010919:Placebos
D021542:Amino Acids, Neutral; D010919:Placebos; D010649:Phenylalanine; D008239:Lysine