Whither Alzheimer's Research?

On June 10, the FDA's advisory panel voted unanimously to recommend approval of Eli Lilly's new monoclonal antibody treatment, donanemab.  This is the same panel where some members quit when the body recommended approval of aducanumab.  While there was some rejoicing over this latest action, much of the reaction was actually muted, as you can see in this article in Nature and this one from the AP. 

So aducanumab (marketed as Aduhelm) has been eclipsed by lecanemab (marketed as Leqembi).  Will donanemab, in turn, eclipse lecanemab?  I read that the two may be better suited to different patients, so probably not.  But all of the monoclonal antibodies (Alzheimer's drugs ending in "mab") are known to cause brain swelling and microhemorrhaging.  As we noted before, a very few subjects died during clinical trials for lecanemab.  Also, according to the AP article, from donanemab.  And, of course, they are all very expensive.

Approval by the advisory panel is not approval by the FDA, but FDA approval of donanemab is likely to follow soon.  We don't yet know what commercial name it will be sold under, nor do we know the price.  But we do know that none of these "mabs" cures Alzheimer's disease, suggesting they are not attacking the disease itself.  Rather, they are alleviating symptoms.

So what does this say about the state of affairs in Alzheimer's research?  

When I was first diagnosed in 2015, there was great optimism about where research was going.  I read an article in a very popular magazine by a doctor who said they should just release one of the prospective treatments without completing the clinical trials, because the treatment was so promising, and people were dying from Alzheimer's anyway.  They didn't name the treatment, but I later concluded it was probably aducanumab.  But when aducanumab appeared to fail dramatically in its disastrous third phase clinical trial, it sent shock waves through the Alzheimer's disease scientific and medical community.  I was surprised by the shock, because I was already a skeptic, and I didn't realize how much hope had been invested in aducanumab.

People are now more wary of premature enthusiasm about new breakthroughs.

And wary they should be.  A long time ago, funding for research assumed that the hope for a cure lay in the amyloid hypothesis.  So attention -- and scientific assumptions -- followed the money.  People with Alzheimer's disease have these amyloid plaques in their brains, so if we remove the plaques, they'll get better.  Right?  ... Right?  

That idea hasn't worked out very well.  As we said in Beating the Dementia Monster, the plaques may actually just be the body's mechanism for fighting the real culprit -- whatever that is.  So the plaques are probably symptoms rather than the disease itself.  And the spectacular success researchers have had in removing the plaques hasn't caused people to be cured.  The progress of the disease may be slowed, but no one gets better by using these treatments.

Then what is the real culprit?  The bacteria that causes gum disease?  The virus that causes shingles?  There is evidence for hypotheses like these, but most of the money has flowed toward dealing with amyloid plaques.  There's work going on with these and other ideas, but there's still a tug-of-war for money.

I was prompted to write about this after reading this article in Vox.  The article didn't say anything we haven't discussed here, but it puts the current disarray in the research world into a more public forum.