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Why the discouraging drug results
Lane Simonian
Posted: Tuesday, January 1, 2013 10:36 AM
Joined: 12/12/2011
Posts: 5158

Drugs currently being used to treat Alzheimer's disease or tested for Alzheimer's disease are mainly or partially missing the target and thus producing discouraging results.  Drugs for Alzheimer's disease either lower acetylcholinesterase activity (Aricept, Exelon, and Galantamine) or inhibit NMDA receptor activity (Namenda).  Drugs being tested for Alzheimer's disease either inhibit the activity of the enzymes that contribute to amyloid plaque formation (gamma secretase and BACE1) or remove some of the plaques.  Here is the problem: phospholipase C activity stimulates y-secretase, BACE1, the formation of plaques, and acetylcholinesterases.  But as the disease progresses, phospholipase C activity declines and so too does acetylcholinesterase activity, y-secretase activity, BACE1 activity, and the deposition of amyloid plaques.  Furthermore, controlling BACE1 or gamma secretase or removing plaques only slows down the formation of peroxynitrites--the real culprit in Alzheimer's disease and likely other forms of dementia as well--and therefore only slows down the progression of Alzheimer's disease early on.  The way to delay the onset of Alzheimer's disease is to inhibit phospholipase C activity and the way to treat it is to use peroxynitrite scavengers.   


Curcumin combined with piperine (to increase is absorption into the bloodstream) is one example of a phenolic compound that will do both.  There are rumors that Merck's BACE-1 inhibitor is a synthetic version of curcumin.  If true, it will work to some degree.  If not, it won't.