Replies to post #186749 on Anavex Life Sciences Corp (AVXL)

[nidan7500]

Stop me if you heard this before:

Is sleep the missing piece of the Alzheimer's puzzle?
The amyloid hypothesis is pretty straightforward: Over time, brain cells can lose their ability to efficiently clear beta-amyloid proteins, forming plaques that disrupt cellular communication (there's a similar hypothesis incorporating tau proteins and other cellular wastes). The thinking goes that a drug aimed at restoring the ability to clear cellular wastes from brain cells could at least stop the progression of Alzheimer's disease. But clinical results in the last decade cast doubt on this simplistic hypothesis, and its accompanying one-and-done drug approach.
Sleep scientists are beginning to understand why. In his recent book Why We Sleep, University of Southern California professor of neuroscience and psychology Dr. Matthew Walker describes the strengthening link between sleep and dementia. Electrical patterns characterizing significant sleep disturbance, especially of non-rapid eye movement (NREM) sleep, "precedes the onset of Alzheimer's disease by several years." After diagnosis, the severity of sleep disturbance correlates with the severity of dementia. It makes sense: NREM sleep is when your brain is most efficient at clearing cellular wastes, including beta-amyloid and tau proteins -- and also at consolidating memories.
The emerging link between Alzheimer's and sleep disturbance provides a more complete picture of disease progression. For instance, beta-amyloid plaques only accumulate in certain regions of the brain (such as those associated with sleep), but not others (such as those associated with memory). This has always stumped scientists. Similarly, the link to sleep might explain why removing plaques from brain cells (the primary mechanism of many experimental Alzheimer's drugs) without improving sleep quality generally fails to improve memory (the endpoints of many Alzheimer's clinical studies). With more than 60% of individuals with dementia also having a co-occurring sleep disorder such as insomnia, it's time to investigate the link more seriously.
Research is being conducted to cement the link between sleep disturbance, plaque formation, and dementia. Encouragingly, if the link holds up, then diagnosing at-risk individuals early on becomes relatively simple, just by using low-cost and non-invasive equipment that reads electrical signals from the brain. Equipment that works in reverse -- sending electrical signals to the brain -- is being studied for its potential to artificially improve sleep quality and memory. In other words, perhaps the future of Alzheimer's treatments resides in devices, not drugs.

It might even make sense to develop combination therapies comprising electrical stimulation of the brain and plaque-clearing drugs to bolster the potential therapeutic effect. That could allow companies such as Biogen to resurrect drugs that failed previous clinical trials, with new trial designs and endpoints.