Developing APOE-targeted epigenome therapy for the treatment of Alzheimer’s disease

Boris Kantor, PhD, Duke University School of Medicine, Durham, NC, talks on the development of a novel APOE-targeted epigenome therapy for late onset Alzheimer’s disease (AD). Through targeted modification of the epigenome, this therapeutic strategy can reduce APOE expression without altering the DNA itself. The therapy uses a lentiviral vector to deliver CRISPR/deactivated Cas9 editing technology, alongside an effector molecule that downregulates gene expression. In vitro evaluation of the epigenome therapy platform in human hiPSC-derived neurons supports the feasibility of the approach, which decreased APOE-mRNA and protein levels. Efforts to target APOEe4 specifically have also been successful. Dr Kantor outlines planned next steps to test the gene-specific technology in in vivo models. This interview took place at the Alzheimer's Association International Conference (AAIC) 2022 in San Diego, CA.