Donanemab removes Alzheimer's plaques: what is special about its target?

Authors: 
Deborah O T Alawode, Amanda J Heslegrave, Nick C Fox, Henrik Zetterberg

A phase 2 clinical trial of donanemab, a humanised immunoglobulin G1 monoclonal antibody that specifically targets N-terminally truncated pyroglutamate-modified amyloid β (AβpE), showed a substantial reduction in Alzheimer's disease-associated cerebral amyloid-plaque load, measured by amyloid positron emission tomography (PET), in the intervention group compared with the placebo group.1 Following the 76 week trial period, donanemab reduced amyloid PET binding by 84·1 centiloids compared with an increase of 0·93 centiloids in the placebo group (from a mean baseline of 108 centiloids in the intervention group vs 101 centiloids in the placebo group). In fact, by week 76, approximately two thirds of the participants receiving donanemab were amyloid-PET negative.