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Finally figuring out Alzheimer's disease
Lane Simonian
Posted: Tuesday, February 8, 2022 8:48 PM
Joined: 12/12/2011
Posts: 5140

I have been trying to figure out Alzheimer's disease for nearly twenty years.  It comes down to this very simple observation:

"The inflammatory mediator peroxynitrite, when generated in excess, may damage cells by oxidizing and nitrating cellular components. Defense against this reactive species may be at the level of prevention of the formation of peroxynitrite, at the level of interception, or at the level of repair of damage caused by peroxynitrite."

Every treatment that slows down the production of peroxynitrite slows down the progression of Alzheimer's disease, but only those treatments which scavenge peroxynitrite and reverse part of the damage it does to the brain largely stabilizes Alzheimer's disease over long periods of time.

Here is a good example, Aricept/donepezil slows down oxidative stress by inhibiting the release of intracellular calcium and Namenda reduces oxidative stress by inhibiting NMDA receptors but both work much better with compounds that also scavenge peroxynitrite and repair part of the damage that it does to the brain:

Adding Chinese herbal medicine to conventional therapy brings cognitive benefits to patients with Alzheimer’s disease: a retrospective analysis

"MMSE change in groups with or without herbal medicine. a Patients with Alzheimer’s disease had a transient improvement in cognitive function with conventional therapy (CT), but declined to a level similar to no treatment after 18 months. CT supplemented with herbal medicine (CT + H) provided additional benefit. The effect from herbal medicines became more pronounced over time. Expected decline of MMSE were calculated by formula produced from previous data. b In subgroup analysis, patients with moderate AD (red lines) were initially more responsive to both CT + H and CT therapies than mild AD (blue lines) patients. Over the course of treatment, CT + H outperformed CT therapy, a substantial deceleration in cognitive decline being observed in patients with moderate AD, while a long-term stabilization effect being observed in the patients with mild AD. MMSE denotes mini-mental state examination."

A number of other examples of this exist.  For instance, compounds in panax ginseng that not only slow down the production of peroxynitrite but also scavenge it and reverse part of its damage led to improvements in cognitive function at 24 weeks that were sustained for two years.  Anavex 2-73 which like Aricept inhibits peroxynitrite formation by reducing the release of intracellular calcium, but unlike Aricept acts as a direct antioxidant largely stabilized cognitive function for three years.  The evidence for other treatments that do the same thing is more short-term but includes aromatherapy and GV-971 (a drug derived from brown algae).

The multiple failures in Alzheimer's drug development was not due to the intractable nature of the disease, it was due to efforts that nibbled around the edges of the disease rather than attacking its core.