Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease

摘要: The failure of several Phase II/III clinical trials in Alzheimer's disease (AD) with drugs targeting β-amyloid accumulation the brain fuelled an increasing interest alternative treatments against tau pathology, including approaches phosphatases/kinases, active and passive immunization, anti-tau aggregation. most advanced aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing equilibrium between reduced (leuco-methylthioninium) oxidized form (MT(+)). MT chloride (methylene blue) was investigated 24-week II trial 321 patients mild to moderate AD that failed show significant positive effects patients, although long-term observations (50 weeks) biomarker studies suggested possible benefit. dose 138 mg/day showed potential benefits on cognitive performance moderately affected cerebral blood flow mildly patients. Further evidence will come from large ongoing III for treatment behavioral variant frontotemporal dementia new this TAI, more bioavailable less toxic at higher doses, called TRx0237. More recently, inhibitors acetylation are being actively pursued based impressive results animal obtained by salsalate, clinically used derivative salicylic acid.