Evidence for a New Genetic Link to Therapeutic Efficacy for Alzheimer...(ificant cost reductions in overall manag...)

To further investigate pharmacogenomic responses of AC-1202 in AD, the effects of APOE4 carriage status and a polymorphism (IDE_7) in the insulin degrading enzyme gene (IDE) on ADAS-Cog scores were evaluated over the study course. In addition to degrading insulin, the Ide protein also degrades amyloid beta peptide and has been implicated in playing a role in Alzheimer's disease.

In the population of patients who were both APOE4(-) and lacked the C/C polymorphism in IDE 7, more pronounced improvements in ADAS-cog scores than those previously reported were observed at each assessment time point (Day 45, 90 and 104). At Day 45 the improvement in ADAS-cog score was 4.18 (p=0.0004), while at Day 90 the difference was 4.73 (p=0.001). Of interest, a significant difference in cognitive test scores of 3.27 was observed two weeks after termination of AC-1202 treatment (p=0.034). This finding suggests that daily administration of AC-1202 may produce lasting effects in those patients with this combination of genotypic markers.

The combination of the E4(-); IDE_7(C/C)(-) genotype is prevalent in approximately 40% of the AD population, so the number of potential responder patients is substantial.

"This pharmacogenomic finding provides both insight into the mechanism of ketone-based therapies for Alzheimer's disease, and also allows for the identification of patients who may respond best to therapy, " said Dr. Samuel Henderson, Research Director at Accera. "This is the first scientific report of the role of IDE and its interaction with APOE on therapeutic efficacy in Alzheimer's disease patients."

The study results will be presented on Wednesday, July 15 under the title, "Evidence of an Interaction Between APOE and IDE in Ketone Body Therapies in Mild to Moderate Alzheimer's Disease." The conference is being h
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