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@ARTICLE{Schlotawa:255144,
      author       = {Schlotawa, Lars and Tyka, Karolina and Kettwig, Matthias
                      and Ahrens-Nicklas, Rebecca C and Baud, Matthias and
                      Berulava, Tea and Brunetti-Pierri, Nicola and Gagne, Alyssa
                      and Herbst, Zackary M and Maguire, Jean A and Monfregola,
                      Jlenia and Pena Centeno, Tonatiuh and Radhakrishnan,
                      Karthikeyan and Schroeder, Sophie and Waxman, Elisa A and
                      Ballabio, Andrea and Dierks, Thomas and Fischer, Andre and
                      French, Deborah L and Gelb, Michael H and Gärtner, Jutta},
      title        = {{D}rug screening identifies tazarotene and bexarotene as
                      therapeutic agents in multiple sulfatase deficiency.},
      journal      = {EMBO molecular medicine},
      volume       = {15},
      number       = {3},
      issn         = {1757-4676},
      address      = {Heidelberg},
      publisher    = {EMBO Press},
      reportid     = {DZNE-2023-00263},
      pages        = {e14837},
      year         = {2023},
      note         = {CC BY},
      abstract     = {Multiple sulfatase deficiency (MSD, MIM #272200) results
                      from pathogenic variants in the SUMF1 gene that impair
                      proper function of the formylglycine-generating enzyme
                      (FGE). FGE is essential for the posttranslational activation
                      of cellular sulfatases. MSD patients display reduced or
                      absent sulfatase activities and, as a result, clinical signs
                      of single sulfatase disorders in a unique combination. Up to
                      date therapeutic options for MSD are limited and mostly
                      palliative. We performed a screen of FDA-approved drugs
                      using immortalized MSD patient fibroblasts. Recovery of
                      arylsulfatase A activity served as the primary readout.
                      Subsequent analysis confirmed that treatment of primary MSD
                      fibroblasts with tazarotene and bexarotene, two retinoids,
                      led to a correction of MSD pathophysiology. Upon treatment,
                      sulfatase activities increased in a dose- and time-dependent
                      manner, reduced glycosaminoglycan content decreased and
                      lysosomal position and size normalized. Treatment of MSD
                      patient derived induced pluripotent stem cells (iPSC)
                      differentiated into neuronal progenitor cells (NPC) resulted
                      in a positive treatment response. Tazarotene and bexarotene
                      act to ultimately increase the stability of FGE variants.
                      The results lay the basis for future research on the
                      development of a first therapeutic option for MSD patients.},
      keywords     = {Humans / Multiple Sulfatase Deficiency Disease: diagnosis /
                      Multiple Sulfatase Deficiency Disease: genetics / Multiple
                      Sulfatase Deficiency Disease: pathology / Bexarotene / Drug
                      Evaluation, Preclinical / Sulfatases: genetics /
                      Oxidoreductases Acting on Sulfur Group Donors / Bexarotene
                      (NLM Chemicals) / drug screening (Other) /
                      formylglycine-generating enzyme (Other) / lysosomal disorder
                      (Other) / retinoids (Other) / sulfatase-modifying factor 1
                      (Other) / tazarotene (NLM Chemicals) / Sulfatases (NLM
                      Chemicals) / SUMF1 protein, human (NLM Chemicals) /
                      Oxidoreductases Acting on Sulfur Group Donors (NLM
                      Chemicals)},
      cin          = {AG Fischer / Bioinformatics and Genome Dynamics Core},
      ddc          = {610},
      cid          = {I:(DE-2719)1410002 / I:(DE-2719)1440016},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9994482},
      pubmed       = {pmid:36789546},
      doi          = {10.15252/emmm.202114837},
      url          = {https://pub.dzne.de/record/255144},
}