Therapeutics: Glutaminyl cyclase (QC); huntingtin (HTT)

In vitro and animal studies suggest inhibiting QC could help treat HD. In mutant HTT-expressing mouse neurons and fly models of HD, siRNA against QC decreased aggregation of mutant HTT and neuronal cell death compared with a control siRNA. In fly and zebrafish models of HD, a newly synthesized small molecule that inhibited QC with an IC50 of 53 nM decreased mutant HTT aggregation and neuronal cell death compared with vehicle. Next steps include evaluating the role of the QC inhibitor in mouse models of HD...