Researchers of a study focused on identifying novel therapeutic targets for Alzheimer’s disease (AD) using Mendelian randomization (MR), a method helpful in repurposing licensed drugs and discovering new therapeutic targets. The researchers integrated druggable genes with blood and brain expression quantitative trait loci (eQTLs) to estimate their causal effects on AD. They validated identified genes through repeat studies with different eQTL data sources and explored potential mechanisms by evaluating the causal relationship between established AD markers.
Out of 5883 unique druggable genes, 33 were identified as potential targets for AD in at least one dataset, and 5 of these were validated in different datasets. Three genes—epoxide hydrolase 2 (EPHX2), SERPINB1, and SIGLEC11—showed significant potential in both blood and brain tissues. EPHX2 was noted to possibly influence the pathogenesis of AD by affecting the hippocampal volume. Consequently, the study underscores the genetic evidence supporting the therapeutic potential of these genes, aiding in prioritizing future drug development for AD.
Reference: Su WM, Gu XJ, Dou M, et al. Systematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2023;94(11):954-961. doi: 10.1136/jnnp-2023-331142.