TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Schwarz, Günter
A1  - Santamaria-Araujo, José Angel
A1  - Wolf, Stefan
A1  - Lee, Heon-Jin
A1  - Adham, Ibrahim M.
A1  - Gröne, Hermann-Josef
A1  - Schwegler, Herbert
A1  - Sass, Jörn Oliver
A1  - Otte, Tanja
A1  - Hänzelmann, Petra
A1  - Mendel, Ralf R.
A1  - Engel, Wolfgang
A1  - Reiss, Jochen
T1  - Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli
JF  - Hum Mol Genet. (Human Molecular Genetics)
N2  - Substitution therapies for orphan genetic diseases, including enzyme replacement methods, are frequently hampered by the limited availability of the required therapeutic substance. We describe the isolation of a pterin intermediate from bacteria that was successfully used for the therapy of a hitherto incurable and lethal disease. Molybdenum cofactor (Moco) deficiency is a pleiotropic genetic disorder characterized by the loss of the molybdenum-dependent enzymes sulphite oxidase, xanthine oxidoreductase and aldehyde oxidase due to mutations in Moco biosynthesis genes. An intermediate of this pathway-'precursor Z'-is more stable than the cofactor itself and has an identical structure in all phyla. Thus, it was overproduced in the bacterium Escherichia coli, purified and used to inject precursor Z-deficient knockout mice that display a phenotype which resembles that of the human deficiency state. Precursor Z-substituted mice reach adulthood and fertility. Biochemical analyses further suggest that the described treatment can lead to the alleviation of most symptoms associated with human Moco deficiency.
Y1  - 2004
SN  - 0964-6906
SS  - 0964-6906
U6  - https://doi.org/10.1093/hmg/ddh136
DO  - https://doi.org/10.1093/hmg/ddh136
PM  - 15115759
VL  - 13
IS  - 12
SP  - 1249
EP  - 1255
PB  - Oxford University Press
ER  -