早老性痴呆药物研究进展课件.ppt
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1、How to accelerate AD research 8/3/20222ContentsCurrent situation of AD1What are big companies doing 2Trends3Perspective48/3/202231 Current situation of ADvPopulation:37 million vCauses:too sophisticatedvMarket drugs:Tarcrine,Donepezil,Rivastigmine,Galanthamine,Huperzine,MemantinevSome social activit
2、ies may correlate with AD,but cannot delay the progress of AD8/3/20224Nature Reviews.2010.7:387-3988/3/202252 What are big companies doingvA big cake attracts a lot of big companies,attention,such as Pfizer,Elan,Merk,Novartis and so on8/3/20226BMC Medicine 2009,7:7 8/3/20227TramiprosatevALZHEMED(Neu
3、rochem Inc.)vThe Phase III trial did not show a beneficial effect on cognition or function,so the development program has been discontinued 8/3/20228Vaccines and antibodiesvAN-1792(Elan)the first-generation amyloid vaccine,Phase II trial was discontinued owing to the development of aseptic meningoen
4、cephalitis in 6%of the patientsvACC-001(Elan)prevent the induction of a toxic cellular immune response,in a Phase II clinical trialvBapineuzumab(Elan/Wyeth):Phase III,monoclonal antibodiesvImmunoglobulin IgIV:Phase III,polyclonal antibodies8/3/202298/3/202210RAGE InhibitorvAmyloid is known to bind t
5、o receptors for advanced glycated endproducts(RAGE)on the surface of cells and at the blood-brain barrier;this binding may contribute to inflammation and neuronal death.vPF-04494700:an orally bioavailable antagonist of RAGE,Phase II 8/3/202211-secretase inhibitorsvTarenflurbil:the enantiomer of the
6、non-steroidal anti-inflammatory drug flurbiprofen,modulates the activity of-secretase,failed in Phase III vSemagacestat:reduction of amyloid peptide generation in blood and cerebrospinal fluid of patients with AD treated with tolerable doses,in Phase III8/3/202212Tau aggregation inhibitorvRember(Met
7、hylene blue):a widely used histology dye,has been shown to interfere with tau aggregation.v Entering Phase III8/3/2022138/3/202214Microtubule stabilizervNAP(AL-108):derived from a natural neurotrophic protein,can be delivered to the central nervous system via intranasal administration.vmarkedly redu
8、ces tau phosphorylation,and preliminary human studies have been encouraging.Now it is in Phase II trial.8/3/202215Dimebon-Pfizerv Phase III trial(Dimebon and Donepezil):failed,but Pfizer now is launching another Phase III trial about dimebon with other AD drugs.NNN8/3/202216vPhase III trials of Gink
9、go biloba,NSAIDs,phenserine,statins,tarenflurbil,tramiprosate,and xaliproden have been completed,none of them demonstrating adequate efficacy.vPhase II trials of dimebon,huperzine A,intravenous immunoglobulin,and methylthioninium chloride were reported at 2008.vNineteen compounds are currently in Ph
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