早老性痴呆药物研究进展.ppt
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1、How to accelerate AD research,2019/3/2,2,Contents,Current situation of AD,1,What are big companies doing,2,Trends,3,Perspective,4,2019/3/2,3,1 Current situation of AD,Population:37 million Causes:too sophisticated Market drugs:Tarcrine,Donepezil,Rivastigmine,Galanthamine,Huperzine,Memantine Some soc
2、ial activities may correlate with AD,but cannot delay the progress of AD,2019/3/2,4,Nature Reviews.2010.7:387-398,2019/3/2,5,2 What are big companies doing,A big cake attracts a lot of big companies,attention,such as Pfizer,Elan,Merk,Novartis and so on,2019/3/2,6,BMC Medicine 2009, 7:7,2019/3/2,7,Tr
3、amiprosate,ALZHEMED(Neurochem Inc.) The Phase III trial did not show a beneficial effect on cognition or function,so the development program has been discontinued,2019/3/2,8,Vaccines and antibodies,AN-1792(Elan)the first-generation amyloid vaccine,Phase II trial was discontinued owing to the develop
4、ment of aseptic meningoencephalitis in 6% of the patients ACC-001(Elan)prevent the induction of a toxic cellular immune response,in a Phase II clinical trial Bapineuzumab (Elan/Wyeth) :Phase III,monoclonal antibodies Immunoglobulin IgIV:Phase III,polyclonal antibodies,2019/3/2,9,2019/3/2,10,RAGE Inh
5、ibitor,Amyloid is known to bind to 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. PF-04494700 :an orally bioavailable antagonist of RAGE,Phase II,2019/3/2,11,-secretase inhibit
6、ors,Tarenflurbil:the enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen,modulates the activity of -secretase,failed in Phase III Semagacestat:reduction of amyloid peptide generation in blood and cerebrospinal fluid of patients with AD treated with tolerable doses, in Phase III,2019/
7、3/2,12,Tau aggregation inhibitor,Rember(Methylene blue):a widely used histology dye, has been shown to interfere with tau aggregation. Entering Phase III,2019/3/2,13,2019/3/2,14,Microtubule stabilizer,NAP (AL-108):derived from a natural neurotrophic protein, can be delivered to the central nervous s
8、ystem via intranasal administration. markedly reduces tau phosphorylation, and preliminary human studies have been encouraging.Now it is in Phase II trial.,2019/3/2,15,Dimebon-Pfizer,Phase III trial(Dimebon and Donepezil): failed,but Pfizer now is launching another Phase III trial about dimebon with
9、 other AD drugs.,2019/3/2,16,Phase III trials of Ginkgo biloba, NSAIDs, phenserine, statins, tarenflurbil, tramiprosate, and xaliproden have been completed, none of them demonstrating adequate efficacy. Phase II trials of dimebon, huperzine A, intravenous immunoglobulin, and methylthioninium chlorid
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- 早老性 痴呆 药物 研究进展
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