Theory behind Alzheimer’s cure remains credible even after drug trial failure

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A drug that was seen as a major test of the leading theory behind Alzheimer’s disease has failed in a large trial of people with mild dementia. Critics of the ‘amyloid hypothesis’, which posits that the disease is triggered by a build-up of amyloid protein in the brain, have seized on the results as evidence of its weakness. But the jury is still out on whether the theory will eventually yield a treatment.

Proponents of the theory note that the particular way in which solanezumab, the drug involved in the trial, works could have led to the failure, rather than a flaw in the hypothesis itself. And many trials are ongoing to test whether solanezumab…could work in people at risk of the disease who have not yet shown symptoms, or even in people with Alzheimer’s, despite the latest negative result.

Lilly’s result may say more about the characteristics of solanezumab than the accuracy of the underlying amyloid hypothesis, says Christian Haass, head of the Munich branch of the German Centre for Neurodegenerative Diseases. The antibody targets soluble forms of amyloid, he points out, so it “could be trapped in the blood without ever reaching the actual target in the brain in sufficient quantities”.

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