Amyloid-b antibodies and edaravone in Alzheimer’s disease

This project aims to evaluate the potential added effect of edaravone, a free radical scavenger, together with amyloid-b antibodies in advanced preclinical Alzheimer’s Disease (AD) models. Treeway is currently performing a Phase 2 study with oral edaravone in AD patients. VUMC has developed advanced neuronal cell models that provide a unique opportunity to evaluate the effects of edaravone and amyloid-b antibodies on the brain.

AD is a serious and growing problem to society with an increasing incidence due to the aging population. Healthcare costs associated with dementia were already 10 billion euros in 2021 in the Netherlands alone. With a combinationtherapy that can halt the disease progression, or significantly slow-down the early symptomatic phase of the disease,complications can be prevented, independent living can be prolonged and quality of life improved. This will have amajor impact on the patient’s personal life, their caregivers and reduce the burden on the healthcare system.

Edaravone acts in different ways to reduce inflammatory and oxidative stress, reducing of Aβ-induced oxidativestress and neurotoxicity. After decades of long and costly research, amyloid antibodies are the only registered drugsthat can modify the disease by efficiently clearing amyloid pathology in AD. Thereby, it is hypothesized that AD canbe improved by targeting both pathways (i.e., amyloid pathology and oxidative stress) that have significantly been associated with AD progression.

Results from this project will substantially improve our understanding on the cellular and molecular basis of neurodegeneration in AD, how and if these pathways are interfered and help us to better design follow-up studies thereby aiding the current unmet need in AD.