Recombinant enzyme therapy for Fabry disease: absence of editing of human alpha-galactosidase A mRNA

Am J Hum Genet. 2003 Jan;72(1):23-31. doi: 10.1086/345309. Epub 2002 Dec 6.


For more than a decade, protein-replacement therapy has been employed successfully for the treatment of Gaucher disease. Recently, a comparable therapy has become available for the related lipid-storage disorder Fabry disease. Two differently produced recombinant alpha-galactosidase A (alpha-gal A) preparations are used independently for this purpose. Agalsidase alpha is obtained from human fibroblasts that have been modified by gene activation; agalsidase beta is obtained from Chinese hamster ovary cells that are transduced with human alpha-gal A cDNA. It has previously been claimed that alpha-gal A mRNA undergoes editing, which may result in coproduction of an edited protein (Phe 396 Tyr) that might have a relevant physiological function. We therefore analyzed the occurrence of alpha-gal A editing, as well as the precise nature, in this respect, of the therapeutic enzymes. No indications were obtained for the existence of editing at the protein or RNA level. Both recombinant enzymes used in therapy are unedited and are capable of functionally correcting cultured fibroblasts from Fabry patients in their excessive globotriaosylceramide accumulation. Although RNA editing is apparently not relevant in the case of alpha-gal A, a thorough analysis of the potential occurrence of editing of transcripts is nevertheless advisable in connection with newly developed protein-replacement therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Fabry Disease / enzymology*
  • Fabry Disease / genetics*
  • Fibroblasts
  • Genetic Therapy*
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Macrophages
  • Molecular Sequence Data
  • RNA Editing / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Trihexosylceramides / metabolism
  • alpha-Galactosidase / chemistry
  • alpha-Galactosidase / genetics*
  • alpha-Galactosidase / metabolism


  • Isoenzymes
  • RNA, Messenger
  • Recombinant Proteins
  • Trihexosylceramides
  • agalsidase alfa
  • globotriaosylceramide
  • alpha-Galactosidase

Associated data

  • OMIM/301500