Failure of Lilly’s Solanezumab Not Seen as Conclusive Proof That Amyloid Theory Is Flawed

Failure of Lilly’s Solanezumab Not Seen as Conclusive Proof That Amyloid Theory Is Flawed
The Alzheimer’s community lamented Eli Lilly's recent announcement that its experimental therapy solanezumab failed to demonstrate efficacy in treating the disease in recent clinical trials. In the announcement, released Nov. 23, Lilly said it would not pursue regulartory approval for the drug. Solanezumab's inability to demonstrate effectiveness in people with mild demential due to Alzheimer’s disease, however, represents more than just a one-drug failure. After one amyloid-targeting drug trial disappointment after the other, some in the Alzheimer's community viewed the solanezumab trial as the final test of the amyloid hypothesis for treating Alzheimer’s disease. Lilly’s announcement gave critics of the amyloid theory plenty of reason for “I told you so” responses. Nevertheless, the hypothesis that amyloid-beta is the villain causing Alzheimer’s disease continues to have its supporters among researchers and caregivers alike, and numerous trials are still testing various drugs that aim to lower the levels of amyloid-beta as a way of preventing cognitive decline in patients. Solanezumab is an antibody that sweeps up soluble single molecules of amyloid proteins from the blood and cerebrospinal fluid, so they cannot go on to form plaques. Both animal studies and earlier human trials of the drug showed promising results. The EXPEDITION3 trial (NCT01900665) recruited more than 2,100 patients with mild Alzheimer’s dementia — a number that would be enough to prove the drug's effectiveness. After 18 months, however, results were only slightly leaning toward a favorable effect of solanezumab — not enou
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3 comments

  1. Timothy Daly says:

    I see that people are still holding onto the amyloid-hypothesis, but in the Nature article, beside the particularities of this perhaps poorly-designed drug trial, there are no actual reasons given for retaining the hypothesis.

    My question to its defenders would be this: what evidence WOULD be enough of a reason to give up this hypothesis?

    Personally, 27 years of research from pretty much every Big Pharma company on the planet on a disease that is not entirely genetically determined in 19 cases out of 20 merits a change in direction. How long will we ignore the epidemiology of modifiable risk factors and start to take them seriously instead of trying to interpret everything in terms of amyloid (or tau)? Forgive me, but I just don’t get it.

  2. The problem is that you cannot proof good science using bad science. Analysis of the past immunotherapeutic studies on Alzheimer’s show that they were based on the wrong assumptions. A result of trying to use without too much thought the knowledge acquired from infectious and cancer immunotherapy to Alzheimer’s, a quite different situation. A number of publications have exposed the errors made in those studies, a result of using incomplete and sometimes misleading information. Yet, few mention those problems, perhaps an indication of not mentioning the rope in the house of the hanged man. To complicate the issue many scientists and the press insist in considering the plaque the villain in Alzheimer’s, despite the evidence that plaque may be protective and that many mentally sound older people have plaque in their brains. Besides, amyloid does not exist in a vacuum, but it interacts with other compounds, thus the whole picture is much more complex. Trying to get rid of the amyloid hypothesis would not help until the past errors are recognized and experimental protocols are designed taking into account those problems. Failure to do so must be considered an exercise of intellectual masochism.

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