Passive Immunotherapy in Alzheimer’s Disease

Abstract

The development of therapeutics for the treatment of Alzheimer’s disease (AD) has been challenged with a myriad of obstacles: an evolving and incomplete understanding of disease etiology and progression, challenges with early diagnosis, multifactorial genetic and environmental factors that contribute to patient variability, and the cost of conducting lengthy clinical trials. One approach that has garnered a significant amount of attention and resources for its potential as a disease modifying approach is passive immunotherapy directed at clearing amyloid-β (Aβ) species, a pathological hallmark of Alzheimer’s disease. While passive immunotherapeutic trials directed at Aβ have not yet demonstrated clinical benefit, they have prompted important advances in the application and understanding of biomarkers, patient selection, novel functional readouts, and safety monitoring. Application of these lessons has enabled more recent clinical trials to incorporate better trial designs and refine inclusion criteria to optimize patient population enrollment. In addition, new passive immunotherapy targets emerging in the clinic have emerged, as well as novel technologies to enhance future antibody therapeutics. Taken together, the advances in research and clinical science have prepared the passive immunotherapy field to advance emerging promising disease modifying treatments in AD.