What works and what doesn ’t work in Alzheimer’s disease? From interventions on risk factors to anti‐amyloid trials

AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disorder with no approved disease‐modifying therapy (DMT). In this review, we summarize the various past approaches taken in an attempt to find treatments capable of altering the long‐term course for individuals with AD, including: translating epidemiological observations into potential treatment options; seeking a single treatment approach across the continuum of AD severity; utilizing biomarkers for assessing target engagement; using biomarkers as early surrogates of clinical efficacy; and enriching study populations to demonstrate ade quate placebo decline during the limited duration of clinical trials. Although targeting the amyloid‐β (Aβ) pathway has been central to the search for an effective DMT, to date, trials of anti‐Aβ monoclonal antibodies have failed to consistently demonstrate significant clinical efficacy. Key learnings from these anti‐Aβ trials, as well as the trials that came before them, have shifted the focus within clinical development programs to identifying target populations thought most likely to benefit from treatments (i.e. individuals at an earlier stage of disease). Other learnings include strategies to increase the likelihood of showing measurable improvements within the clinical trial setting by better predicting decline in placebo participants, as well as developing measures to quantify the needed treatment exposure (e.g. higher doses). Given the complexity asso...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research