Journal of Clinical Toxicology
Open Access

Department of Genetics and Medicine, Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, 80078 Naples, Italy

Publications

• Review Article   
  Tamoxifen for the Treatment of Batten Disease
  Author(s): Chiara Soldati, Sandro Montefusco, Valentina Bouché and Diego Luis Medina*
  
  Batten Diseases (BDs) are a group of lysosomal storage disorders characterized by seizure, visual loss, and cognitive and motor deterioration, and represent the most common forms of neurodegeneration in children. By phenotypic screening, we recently discovered a novel accumulation of Globotriaosylceramide (Gb3) in cellular and murine models of two subtypes of BD, namely CLN3 and CLN7 diseases, which together account for almost 60% of all BD patients. We used fluorescent-conjugated bacterial toxins to label Gb3 and developed a cell-based High Content Imaging (HCI) screening assay that resulted in the repurposing of the FDA-approved hit tamoxifen. Interestingly, tamoxifen showed in vitro and in vivo the activity to ameliorate BD phenotypes through a mechanism that, at least in part, involves the activation of the Transcription Factor EB (TFEB), a master gene of lysosom.. View More»
  DOI: 10.35248/2161-0495.22.12.518

  Abstract HTML PDF