Use of Repurposed Compounds for the Treatment of Alzheimer ’s Disease

There are no effective treatments for Alzheimer ’s disease (AD), a progressive brain disease that slowly destroys a person’s memory, cognitive skills and ability to carry out the simplest tasks. AD affects more than 5 million individuals in the United States and ranks as the sixth leading cause of death. The ε4 allele of the apolipoprotein-E (APOE) gene is the strongest genetic risk factor for sporadic or late-onset AD. Heterozygous carriers of the ε4 allele are at three-to-four times greater risk; homozygous carriers are at ten times greater risk. In fact, APOE ε4 carriers accumulate AD neuropathology early in adulthood with earlier age onset of AD compared with ε4 non-carriers.Researchers at the National Institute on Aging (NIA) identified a brain proteomic signature comprised of 25 proteins that may drive the risk for developing AD in young APOE ε4 carriers. NIA researchers further identified compounds that target proteins in this AD proteomic signature and rescue molecular abnormalities associated with AD. Specifically, the STAT3 inhibitors TTI-101 and hydroxychloroquine rescued three specific AD phenotypes in cell culture-based phenotypi c screens: (1) lipopolysaccharide (LPS)-induced neuroinflammation; (2) tau phosphorylation; and (3) Aβ secretion/Aβ clearance. Dasatinib, a YES1/FYN inhibitor, lowered tau phosphorylation. These findings reveal that TT1-101, hydroxychloroquine and Dasatinib – among other approved and experimenta l drugs – may be repurposed...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research