More on the Aduhelm Backlash and Something Interesting ... to Nerds

****I've been working to figure MailChimp out, and make the blog post emails more readable.  This should be an improvement over yesterday's post.****

We said in yesterday's post that some insurance companies will likely balk at Biogen's high price for Aduhelm.  Last week, insurer Point32Health indicated that they were unlikely to cover Aduhelm, at least at the proposed pricing.  Point32Health was formed as a merger between Tufts Health Plan and Harvard Pilgrim Health care, and it serves 2.2 million members in New England.  Point32Health's president, Dr. Michael Sherman, told the Boston Globe that Biogen was favoring corporate profits over patient interests.  He believes the price should be a tenth of what Biogen is starting with.

As we discussed in Beating the Dementia Monster, Aduhelm is one of several treatments that can remove amyloid plaques from the brain.  The prevailing understanding of the disease for a long time was the idea that the principal characteristic of the disease was the accumulation of amyloid plaques on nerve cells.  An over-simplification: the plaques interfere with the functions of brain cells and interfere with communication between cells.  The plaques eventually kill the cells.  This was called the amyloid hypothesis.  Alternatively the tau hypothesis focuses tau protein pathology in the microtubules. 

At least in its original form, the Amyloid hypothesis did not account for the tau tangles that Alois Alzheimer saw with his microscope in the brain of a 55-year old German hausefrau, Auguste Deter.  (We discuss tau tangles in Beating the Dementia Monster.)  This was, of course, during her autopsy.  Nevertheless, an important theme of the search for an Alzheimer's drug has been that an effective drug must remove the amyloid plaques.  Ban2401 is one of several other treatments that can do this.  The expectation is that, if you remove the amyloid plaques, you both stop progress of the disease and improve cognition.  

But it hasn't worked out that way.  Ban2401 has not, at least immediately, improved cognition after removing the plaques.  Aduhelm removes plaques too, but there remains a question as to whether it is effectively improving cognition.  Not all researchers believe the Amyloid hypothesis explains Alzheimer's disease, and not all think that plaque removal is the path to a successful treatment.  Some believe that the FDA's approval of Aduhelm encourages us to take our eyes off the ball ... finding a fundamentally different approach to understanding the disease and its treatment.

In an odd way, the controversy over Aducanumab has contributed to the search for alternatives.  There has been some improvement in cognition from the treatments that remove plaques, but not nearly as much as predicted or hoped.  So perhaps the plaques play a more tangential role in the disease that we haven't anticipated.  We discussed this in Beating the Dementia Monster, but this idea is finding new strength in aducanumab research.

Dr. Bart De Strooper, who leads the U.K. Dementia Research Institute at University College London, speaks out against a simple cause-effect relationship between amyloid accumulation and cognitive decline.  Instead, it may be that amyloid accumulation triggers a series of disease processes.  This is called the amyloid cascade hypothesis, and it too has its detractors.

Professor Takeshi Iwatsubo of the University of Tokyo suggests that plaque removal treatments succeed when there is a corresponding reduction in tau tangles, which is not always the case.  He suggests, however, that in the case of the aducanumab trial that did marginally improve cognition, it may be that the load of tau tangles was also lowered during treatment.  Why?  Do we need to understand more about the relationship between the collapse of microtubules we see in the tau hypothesis and the role of beta amyloid in Alzheimer's disease?   

These researchers say "yes."  We still have work to do.