Insanity is doing the same thing over and
over again and expecting different results.
– Variously Attributed
[This blog was written and published on Monday July 20th, two days prior to the announcement of the results of Eli Lilly’s clinical trials of solanezumab for Alzheimer’s.]
Until now, there have been only two globally-approved drugs for Alzheimer’s disease (Aricept and Namenda), and neither of these have been shown to slow, let alone stop or reverse Alzheimer’s. Most current clinical hopes have been pinned to various attempts to use monoclonal antibodies to attack beta amyloid in the brain, and none of these have been shown to slow, let alone stop or reverse Alzheimer’s disease either.
At the current meeting of the Alzheimer’s Association (July 18-23, Washington, DC) there has been growing interest in the latest clinical trial of this disappointing approach, as Eli Lily announces (on Wednesday July 22nd) the latest results of using solanezumab (also called “Soli”), a drug which was a disappointment in its initial clinical trials. Nevertheless, and to the surprise of many, the FDA gave Eli Lilly permission to continue their phase 3 trials and expectations increased the price of the Eli Lilly stock as the upcoming announcement of the results approaches. Unfortunately (not only for the company, but for all of us), the results will be equivocal at best and certainly won’t show that we can slow, stop, or reverse Alzheimer’s.
Why don’t any of the drugs that target beta amyloid have any effect on the underlying disease process? Why have all of the monoclonal antibody drugs — with Soli just the latest heartbreaking therapeutic (or non-therapeutic) disappointment — failed to stop the disease?
The unspoken assumption has been that beta amyloid “causes” Alzheimer’s.
Oddly enough, the assumption is false: beta amyloid doesn’t cause Alzheimer’s disease. Small wonder then when our attempts intervene in the wrong target fail every time. Mind you, beta amyloid is clearly implicated in the pathology and it clearly plays an important role, but to say that is “causes” Alzheimer’s is to confuse cause and effect. If we have a patient with an infection, a high fever, and an elevated white blood cell count, we wouldn’t blame the fever or the white cells for the infection. Likewise, it would be silly (and dangerous) to “treat” the infection by simply removing the patient’s white cells. Yet this is the same sort of logical error we routinely make with Alzheimer’s disease. We know that almost all cases of Alzheimer’s disease show amyloid deposits at autopsy (or now, using other tests, even in living patients with Alzheimer’s), and we know that amyloid deposits can damage neurons, but to automatically conclude that that’s the entire ball game is to go well beyond reality and enter the realms of wishful thinking (or insanity, if we were to believe the quote given above).
None of the clinical trials aimed at removing beta amyloid have ever shown efficacy.
The problem is that amyloid is the wrong target and monoclonal antibodies against amyloid are the wrong intervention. The current failure of solanezumab is simply one more in the list of such failures. If trying the same failed approach over-and-over is insanity, then sanity would be to try a new intervention, an intervention based on a sophisticated appreciation of the actual clinical pathology. In my new book The Telomerase Revolution, I not only discuss that more sophisticated view of the pathology, but how we plan to intervene in a more rational and effective fashion.