Tau-directed approaches for the treatment of Alzheimer's disease: focus on leuco-methylthioninium

Expert Review of Neurotherapeutics
Davide SeripaFrancesco Panza

Abstract

Small molecular weight compounds able to inhibit formation of tau oligomers and fibrils have already been tested for Alzheimer's 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.

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Citations

Apr 23, 2016·Biomolecules·Miguel MedinaJesús Avila
Sep 30, 2016·Expert Opinion on Emerging Drugs·Francesco PanzaGiancarlo Logroscino
Mar 30, 2017·Journal of Geriatric Psychiatry and Neurology·Massimiliano BuoliAlfredo Carlo Altamura
Apr 12, 2019·Expert Review of Neurotherapeutics·Francesco PanzaCarlo Colosimo
Jun 6, 2019·Expert Opinion on Drug Discovery·Juan F GonzálezJose María Sánchez-Montero
Mar 24, 2020·Nature Reviews. Neurology·Francesco PanzaBruno P Imbimbo
Aug 11, 2020·Expert Opinion on Emerging Drugs·Madia LozuponeFrancesco Panza
Sep 9, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sruti RayaproluNicholas T Seyfried
Jul 25, 2019·Der Nervenarzt·Klaus FließbachAnja Schneider
Mar 27, 2020·Saudi Journal of Biological Sciences·Richard L JayarajRami Beiram
Aug 18, 2021·The Protein Journal·Dan WangYongqi Huang
Sep 19, 2019·ACS Chemical Neuroscience·Yam Nath PaudelMohd Farooq Shaikh
Oct 16, 2021·Der Nervenarzt·Gesine RespondekGünter U Höglinger

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