In the quest to treat Alzheimer’s, a complex and devastating disease, researchers have long struggled to find effective therapies. The recent FDA approval of lecanemab brings hope.
This antibody treatment targets a specific form of the amyloid-beta (Aβ) peptide, which is believed to be one of the major culprits behind Alzheimer’s.
A new study from The Rockefeller University delves into the mechanism by which lecanemab seems to work, potentially offering new pathways for treating not only Alzheimer’s but a variety of other diseases as well.
The Problem
Alzheimer’s is a global health crisis with growing numbers of cases. Current therapies, such as aducanumab, have significant side effects like amyloid-related imaging abnormalities (ARIA), which include edema and hemorrhage.
Lecanemab, however, has shown significantly fewer instances of ARIA—raising questions about its mechanism of action.
The Mechanism Behind Lecanemab
The study, led by Erin Norris, focuses on protofibrils, a specific type of Aβ clump. Norris and her team found that these protofibrils activate the plasma contact system, a backup for the primary coagulation system in the body.
Activation of this system has been linked to Alzheimer’s-associated cerebrovascular abnormalities, such as hemorrhage and decreased blood flow.
Lecanemab, by targeting these protofibrils, interferes with this activation process, likely explaining its lower side effect profile.
The Promise of a New Therapy—3E8
The study opens up new treatment avenues.
Norris and Sidney Strickland, co-senior author of the study, have developed an antibody called 3E8 that blocks the activation of the plasma contact system by targeting high molecular weight kininogen (HK).
This treatment could be used alone or in conjunction with anti-Aβ therapies like lecanemab, potentially eliminating ARIA as a side effect.
The researchers also note that dysregulation of the contact system is common in other diseases, such as COVID, sickle cell anemia, sepsis, and cancer.
This means that therapies like 3E8 could have broad applications beyond Alzheimer’s.
The research provides crucial insights into the workings of lecanemab, explaining its lower rate of side effects compared to other Alzheimer’s therapies.
It also introduces a potential new therapeutic avenue in the form of 3E8, which could either complement existing treatments or offer a new strategy for tackling Alzheimer’s and other diseases involving the dysregulation of the plasma contact system.
If you care about brain health, please read studies about vitamin D deficiency linked to Alzheimer’s and vascular dementia, and higher magnesium intake could help benefit brain health.
For more information about brain health, please see recent studies about antioxidants that could help reduce dementia risk, and coconut oil could help improve cognitive function in Alzheimer’s.
The study was published in PNAS.
Follow us on Twitter for more articles about this topic.
Copyright © 2023 Knowridge Science Report. All rights reserved.
