ApoE4 is the strongest genetic risk factor for late-onset Alzheimer's Disease. Individuals carry one of three variants of the ApoE gene: ApoE2, ApoE3, or ApoE4.
Carriers of the ApoE4 allele have an increased risk of developing Alzheimer's at an earlier age-of-onset and increased rate of progression in a gene dose dependent manner. 65–80% of all Alzheimer's Disease patients have at least one ApoE4 allele and 20% of all Alzheimer's Disease patients are homozygotes for ApoE4.
One of our programs aims to treat ApoE4 carriers with Alzheimer's disease (AD) and stems from work of Dr. Robert Mahley and Yadong Huang from the Gladstone Institutes. Their work led to the identification of unique structural features of ApoE4 that drive ApoE4-specific biology. E-Scape is expanding on this fundamental biology to develop small-molecule allosteric modulators that alter ApoE4 protein structure to restore normal ApoE function.