Our Research

From Risk to Remedy: ApoE4-Targeted Solutions for Alzheimer’s Disease

Homozygosity for the APOE ε4 allele increases the risk of Alzheimer’s disease by more than 12-fold compared to the common ε3;ε3 genotype. This heightened risk is closely tied to APOE ε4’s disruption of autophagy, a natural cellular clearance pathway. Our team uncovered that ApoE4 protein binds directly to “CLEAR” promoter elements of key autophagy genes, silencing their expression.

Using an integrated drug discovery approach, we pinpointed a druggable site on ApoE4 and screened thousands of lead-like compounds. This effort revealed small molecules capable of blocking ApoE4’s DNA binding activity. These candidates were validated both in vitro and in vivo, including in humanized ApoE4 mouse models.

Among them, CBA2 emerged as a breakthrough—restoring transcription of autophagy genes and preventing amyloid-like aggregation in a C. elegans Alzheimer’s model.

This discovery offers proof-of-principle that targeting ApoE4 directly can restore lysosomal autophagy, opening a novel therapeutic strategy against Alzheimer’s and related neurodegenerative diseases.

GFAP Inhibition: A Novel Strategy Against Alzheimer’s and Parkinson’s Disease

At AR Therapeutics, we have identified Glial Fibrillary Acidic Protein (GFAP) as both a biomarker and a powerful new drug target for Alzheimer’s disease (AD). GFAP plays a central role in driving neuroinflammation and contributes directly to the formation of amyloid plaques and tau tangles, the toxic hallmarks of AD, and also in Parkinson’s Disease (PD). By targeting GFAP, we are pioneering a new therapeutic approach that moves beyond traditional amyloid- or tau-focused strategies.

Our discovery of MSR1, a novel small-molecule inhibitor of GFAP, marks a significant breakthrough in Alzheimer’s drug development. MSR1 has shown the ability to block GFAP-mediated pathways, reduce both amyloid and tau aggregation, and restore healthy cellular balance. These findings position MSR1 as a first-in-class therapeutic candidate with the potential to slow, halt, or even reverse disease progression.

This innovative approach establishes GFAP inhibition as a transformative new strategy against Alzheimer’s and related neurodegenerative disorders—placing AR Therapeutics at the forefront of next-generation drug discovery.