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

In this review, we summarize past approaches to finding an anti ‐amyloid‐β monoclonal antibody capable of altering the disease course in Alzheimer's disease (AD). Key learnings from the field have helped shape the current AD clinical development programs, including translating epidemiological observations into potential treatment options, evaluating therapi es across the AD continuum, using biomarkers to assess target engagement and as a surrogate of efficacy, and enriching study populations. Because of the underlying complex pathophysiology of AD, disease‐modifying therapies targeting both amyloid‐dependent and ‐independent mechanisms may be nee ded to provide clinical benefit across the disease continuum. 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‐tre atment 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 adequate placebo decline during the limited duration of clinical trials. Although targe ting the amyloid‐β (Aβ) pathway has been central to the search f...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research