Alzheimer's Disease Is A Asshole, According To Science

Te Encanta la Pinche Ciencia!

Two weeks ago, yet ANOTHER huge Phase III study trying to find a treatment for Alzheimer's Disease (AD) tanked big time. Biogen and its partner Eisai let the world know that their experimental drug Aducanumab failed, and right away, Biogen lost almost twenty billion dollars in market value. This was a drug that had promising Phase II data, but that was going after the disease in the same way as many other drugs that had tried and failed before it. What went wrong? I'm not an expert in the field, but I really think it's the wrong target. More on that later.

Of all the diseases out there, Alzheimer's has to score pretty high in the fucked up rankings. It's a devastating illness, insidious in the gradual way it destroys a person's life. It steals your memories, it changes your personality, it destroys your independence, it shatters your relationships and eventually it also takes your life. It's not only devastating to the patient but also to their family, friends and caregivers in ways that few other diseases are. Unlike cancer or heart disease, there are no good options for Alzheimer's patients. The five approved drugs only help symptoms but don't treat the actual disease. Because of that and because with an aging population it's a potential goldmine for pharma companies, drug development money is thrown at it faster than the actual science we understand about the disease would dictate. Before we get back to the failed drug, let's go into a little Wonksplainer on what Alzheimer's disease is.

Um ...

Well, we don't actually know!

Research shows two key features of Alzheimer's disease, but we don't know if they are what cause the symptoms and eventual death. One is accumulation of beta-amyloid protein in the brain and the other is formation of tangled bundles of fibers within neurons. The former are called "plaques" and accumulate in between the neurons. The latter are fibers that normally work to create the architecture of the brain cells' connections and are made up primarily of a protein called "tau." Both of these abnormal situations, accumulation of beta-amyloid and messed up tangles of tau, occur in the parts of the brain related to memory. As a result, most attempts at experimental treatments target approaches to get rid of the accumulation of beta-amyloid or to interfere with the tau protein, even though we don't know if those CAUSE the disease or occur BECAUSE of the disease.

John Lief MD  

Alzheimer's was discovered in 1906 by German psychiatrist Alois Alzheimer and later on the disease was named after him. The disease is divided into four stages, basically broken up by how bad the symptoms are. First you are "pre-dementia" and signs are pretty subtle so you may not even know you have AD. The biggest symptomatic flag here is apathy, so if you just went by that, every teenager would be suspect for AD. Next up is the cleverly named "early" stage. Basically, now you are legit showing symptoms but not big time issues yet. Maybe you forget some new memories here and there or have issues learning new things. Advance from "early" to "moderate" AD and here you can really tell you have the disease. Now you have problems with language, forgetting words and replacing them with incorrect ones, mobility issues start happening, and behavioral problems start. Finally, you reach "advanced" AD where you are totally dependent on caregivers. Language issues are severe, and you eventually end up bedridden. Death typically comes from a secondary disease or condition like pneumonia or an infection.

Although it's very difficult to diagnose in the pre-dementia or even the early phase, once the diagnosis is confirmed, the outlook is bleak. Life expectancy ranges from three to ten years after the diagnosis is made. One study estimates that in the US AD prevalence was two percent in 2000 both overall and in the 65–74 age group. That goes up with age, with 19 percent in the 75–84 year-olds and then a whopping 42 percent people older than 84. Clearly, as the baby boomer population continues to age we will see more and more AD and the burden to society, let alone the individual heartbreak each patient and their family and friends will endure. The growing volume of patients and the lack of options to treat the disease are why pharma continuously bangs its head against the wall trying new drugs, even with the abysmal failure rate.

From 1997 to 2017 the biotech/pharma industry had 146 failed clinical studies in AD. Now, not all were big Phase III studies like the recent Biogen failure (1300 patients!), but man , that's a desert of drug development! In 2018 there were another six big Phase III failures. All of these are going after the two approaches I mentioned early in the story and that's pretty much the guy looking for his car keys under the lamp because "that is where the light is." Rather than spending those hundreds of millions (probably billions by now) on basic research to learn more about AD pathophysiology and come up with a new approach, pharma keeps swinging and missing. After the massive failure and $20 billion loss in value, Biogen did decide to move on, but want to know what Eisai, their partner is planning next? ANOTHER big Phase III study with the same drug. FFS!

This has been your Wonkette science lesson on WTF is going on with Alzheimer's treatment drugs, and why we think maybe big pharma should try a new strategy. We are just saying!

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