A Genome-Wide Association Study in Human Lymphoblastoid Cells Supports Safety of Mitochondrial Complex I Inhibitor.
Gao H, Tripathi U, Trushin S et al.
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Novel therapeutic strategies for Alzheimer's disease (AD) are of the greatest priority given the consistent failure of recent clinical trials focused on Aβ or pTau. Earlier, we demonstrated that mild mitochondrial complex I inhibitor CP2 blocks neurodegeneration and cognitive decline in multiple mouse models of AD. To evaluate the safety of CP2 in humans, we performed a genome-wide association study (GWAS) using 196 lymphoblastoid cell lines and identified 11 SNP loci and 64 mRNA expression probe sets that potentially associate with CP2 susceptibility. Using primary mouse neurons and pharmacokinetic study, we show that CP2 is generally safe at a therapeutic dose.
36 African American lymphoblastoid cell lines, 84 European ancestry lymphoblastoid cell lines, 76 Han Chinese ancestry lymphoblastoid cell lines
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