@article{SchwarzSantamariaAraujoWolfetal.2004,
  author    = {G{\"u}nter Schwarz and Jos{\´e} Angel Santamaria-Araujo and Stefan Wolf and Heon-Jin Lee and Ibrahim M. Adham and Hermann-Josef Gr{\"o}ne and Herbert Schwegler and J{\"o}rn Oliver Sass and Tanja Otte and Petra H{\"a}nzelmann and Ralf R. Mendel and Wolfgang Engel and Jochen Reiss},
  title     = {Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli},
  series   = {Hum Mol Genet. (Human Molecular Genetics)},
  volume    = {13},
  number    = {12},
  publisher = {Oxford University Press},
  issn      = {0964-6906},
  doi       = {10.1093/hmg/ddh136},
  pages     = {1249 -- 1255},
  year      = {2004},
  abstract  = {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.},
  language  = {en}
}