Ornit Chiba-Falek, PhD, Duke University School of Medicine, Durham, NC, shares insights into a novel epigenome therapy under investigation for the treatment of late onset Alzheimer’s disease (LOAD), that reduces APOE expression generally and the APOEe4 allele specifically. The therapy uses CRISPR/dCas9 gene editing technology designed to target regulatory elements within the APOE promoter/intron 1 region and the exon 4 sequence overlapping the SNP that defines the APOEe4 allele. It was then evaluated in vitro using human hiPSC-derived neurons and in vivo in mice brains using a dCas9-repressor vector and the GFP reporter gene. In vitro, APOE-mRNA and protein overall levels were reduced in hiPSC-derived neurons with the e4 allele while there was no effect in isogenic hiPSC-derived neurons homozygous for the e3 allele. In the mice, there was a 50-70% decrease in GFP expression, representing promising preliminary data for this APOE-targeted epigenome therapy. This interview took place at the Clinical Trials on Alzheimer’s Disease Congress 2022 in San Francisco.
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Prof. Chiba-Falek reports the following disclosures: -Co-Founder at CLAIRIgene -CLAIRIgene is negotiating the licensing of the technology developed in this study