Anti-amyloid antibody therapies in Alzheimer's disease

Perneczky, Robert; Jessen, Frank; Grimmer, Timo; Levin, Johannes; Floeel, Agnes; Peters, Oliver und Froelich, Lutz (2023): Anti-amyloid antibody therapies in Alzheimer's disease. In: Brain, Bd. 146, Nr. 3: S. 842-849

Abstract

After years of failed attempts to develop a disease-modifying therapy for Alzheimer's disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-beta protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-beta lowering on PET also underpin the positive results of the trial. In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer's disease failed. We compare the safety profiles of the different antibodies and highlight cautionary measures for their routine clinical use. Last, we discuss the role of blood-based biomarkers in transforming the clinical care pathway to facilitate the uptake of antibody treatments, proposing an integrated case-finding and treatment model crossing the different healthcare sectors. Taken together, a real breakthrough may have been achieved by proving that amyloid-beta reduction results in clinical benefits, rather than just biomarker changes. At the same time, routine use of the new generation of drugs will show if statistical efficacy translates into clinically meaningful change. This may just be the beginning of a new era of Alzheimer's disease drug development. Perneczky et al. examine why previous trials of disease-modifying treatments for Alzheimer's disease failed and why lecanemab fared differently. They discuss what the results may mean for patients, and argue that healthcare systems must adapt to facilitate rapid and safe uptake of anti-amyloid antibody treatment.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198