Lecanemab and other treatments: Glimmers of hope for alzheimer’s patients

Abstract

Lecanemab and other treatments: Glimmers of hope for alzheimer’s patients Effective treatments for amyloid-associated neurological diseases are desperately needed; H. Robert Guy, CEO of Amyloid Research Consultants, talks us through the obstacles and opportunities associated with structure-based drug design. The FDA recently approved an antibody drug, Lecanemab, aka Leqembi, that slows neuronal degeneration caused by Alzheimer’s Disease (AD). Granted, Lecanemab is no miracle drug: it is not a cure, it can have deleterious side effects, and it is expensive. Nonetheless, it is the first antibody treatment for AD to be efficacious. Lecanemab antibodies were developed to target amyloid beta (Aβ), long suspected of being a major cause of AD and a prime constituent of amyloid plaques. This development was a surprise since previous attempts to use antibodies to Aβ fibrils have failed. Numerous researchers have long argued that Aβ fibrils are not the primary culprit; smaller Aβ assemblies called oligomers are more toxic, appear earlier, and can interact with membranes to increase their permeability to calcium ions. When an electric impulse called an action potential reaches a presynaptic terminal, it triggers the entry of calcium ions that stimulate the release of neurotransmitters. Interference by Aβ with this process can have devastating consequences.