Why Alzheimer’s Drugs Haven’t Improved In Decades.

I’ve talked elsewhere about the staggering disappointment of the last few decades in the realm of Alzheimer’s Disease (AD) research. Long story short: in the late 20th Century the research community was certain we’d have a cure by now. We don’t. In fact, the treatment you’re given today is same as it was then, and the benefits are marginal at best.

Why is this?

Imagine you have a car and the brakes go out. The only way to stop is to ram into things.

So you end up with lots of dents in your bumper.

What’s the primary issue here? Is it the dents in your bumper, or the fact that you have no brakes?

And would spending trillions of dollars to describe the formation of a dent at the atomic level bring you any closer to figuring out why those dents are there?

With AD, we’ve spent the last several decades characterizing the formation of dents at a ridiculous amount of detail. This is why the prevailing theories of Alzheimer’s Disease have not improved in that time, since improving the detail of our dent descriptions will never bring us any closer to understanding how those dents got there.

We’ve also spent the last several decades trying to fix our problem by fixing the dents. In this case, by trying to find drugs that fix the dents. While continuing to ignore the whole brake issue.

It gets worse, though.

Imagine that, in order to reduce the amount of dentage (not a real word) to your bumper, you place 6 inches of rubber padding on your front bumper. The rubber, in this case, is an attempt to minimize the damage from the primary problem (your inability to stop the car with brakes). The added rubber padding is also a consequence of having no brakes, and wouldn’t be seen on cars with functioning brakes.

Some of the drugs that have been developed, and are still being developed, are designed to remove the rubber. In other words, not only do they ignore the fundamental problem (in the case of AD, drugs CAN’T target the fundamental problem), but they may actually be targeting the brain’s attempt to mitigate that problem.

p.s. – I regret to inform that this problem of dent distraction isn’t just limited to AD research.

p.p.s. – okay, there’s more. I hate it, too.

Imagine that you try to figure out your dent issue by designing a bumper that dents really easily. Perhaps you make it out of tin foil. And then you put it on a car with perfectly fine brakes. And then you test all of your potential solutions on your tin-foil-bumpered car with perfectly normal brakes.

You create some bumper-additive that strengthens the tin foil and leads to less denting, publish it in a big journal, and bask in the headlines claiming you’re destined for a Nobel Prize. You get billions of dollars to fund the research and development of your breakthrough additive but alas, when it’s tested on the brake-deficient cars with regular bumpers, it makes no difference.

Yet, since finding a solution that leads to fewer dents in tin foil bumpers is associated with accolades and financial prosperity, the race to find the next dent-reducing additive in tin-foil-bumpered cars with perfectly normal brakes continues undaunted.

(In other words, we should not expect the drugs that work in our animal models to work in actual real-world cases of AD in humans, since those animals are modeling an entirely different thing. Yet, we should not expect this foolishness to end until compounds that yield improvements in animal models are no longer heralded as the breakthrough we’ve all been waiting for and generate billions more dollars in funding.

Imagine if we put just a fraction of those resources into understanding how to best fix those brakes….)