Tuesday, August 17, 2010

Another nail in the coffin for the Alzheimer's amyloid hypothesis

Researchers bet careers, and pharmas bet billions, that amyloid plaques caused neuronal dysfunction in Alzheimer's disease. If the plaques could be prevented, you could prevent the disease.

Those bets have been going bad over the past four years. Today Lilly lost another bundle ....
Lilly Halts Alzheimer’s Drug Trial - Prescriptions Blog - NYTimes.com
... semagacestat, did not slow progression of the disease and was associated with a worsening of cognition and the ability to perform the tasks of daily living....
... The failures, and particularly this newest one by Lilly, could raise questions about the validity of the prevailing theory about Alzheimer’s, which is that the disease is caused by the accumulation of so-called amyloid beta plaques in the brain. 
 Lilly’s drug was designed to reduce the body’s production of the plaques by inhibiting the activity of an enzyme, called gamma secretase, that is believed to play an important role in formation of the plaque...
The contrary hypothesis was that the characteristic amyloid plaques of Alzheimer's disease were either a consequence of the disease process, or perhaps even some sort of protective measure. That hypothesis has been getting more support.

This latest result is just one example of all the recent bad news on delaying age-related dementia in general, and Alzheimer's disease in particular. We now know that "mental exercise", "social prophylaxis" and so on don't delay disease onset. We have shown that most treatment medications are, at best, marginally effective and poorly tolerated. We have no preventive meds -- estrogen, statins, non-steroidals and so on all are unimpressive.

We do know that head injuries are bad - worse than we imagined. Not only are concussions associated with Alzheimer's dementia, they're also associated with motor neuron disease. Most contacts sports, including American football and "soccer" will look very different in 10 years.

We believe, bizarrely, that exercise really does preserve the brain. We don't have a solid mechanism for that.

We also have tests that can diagnose Alzheimer's early, which is a good way to ensure you'll never be able to buy long term care insurance. Otherwise the tests look pretty pointless.

We need some good news. Forget the blather about social security -- that's not the crisis. That's just a GOP distraction. The crisis is pre-dementia and dementia in an aging post-industrial America.

No comments: