Tau-directed approaches for the treatment of Alzheimers disease: Focus on leuco-methylthioninium

Antonio Daniele, Davide Seripa, Vincenzo Solfrizzi, Bruno P. Imbimbo, Andrea Santamato, Madia Lozupone, Giovanni Zuliani, Antonio Greco, Giancarlo Logroscino, Francesco Panza

Research output: Contribution to journalArticle

24 Citations (Scopus)


Small molecular weight compounds able to inhibit formation of tau oligomers and fibrils have already been tested for Alzheimers disease (AD) treatment. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT+). MT chloride (also known as methylene blue) was investigated in a 24-week Phase II study in 321 mild-to-moderate AD patients at the doses of 69, 138, and 228 mg/day. This trial failed to show significant positive effects of MT in the overall patient population. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected patients and cerebral blood flow in mildly affected patients. A follow-up compound (TRx0237) claimed to be more bioavailable and less toxic than MT, is now being developed. Phase III clinical trials on this novel TAI in AD and in the behavioral variant of frontotemporal dementia are underway.
Original languageEnglish
Pages (from-to)259-277
Number of pages19
Publication statusPublished - 2016


  • Alzheimer Disease
  • Alzheimer's disease
  • Clinical Trials as Topic
  • Humans
  • Methylene Blue
  • Neurology (clinical)
  • Neuroscience (all)
  • Pharmacology (medical)
  • TRx0237
  • dementia
  • immunotherapy
  • leucomethylthioninium
  • methylthioninium
  • microtubule-stabilizing agents
  • tau Proteins
  • tau aggregation inhibitors
  • tau phosphorylation inhibitors
  • tau protein


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