Therapeutics: Ataxia telangiectasia mutated (ATM); huntington (HTT)

In vitro and mouse studies suggest ATM inhibitors could help treat HD. In a mouse model of HD, ATM knockout decreased behavioral deficits and the number of mutant HTT aggregates in the brain compared with normal ATM expression. In mutant HTT-expressing rat striatal neurons and striatial neurons generated from HD patient-derived induced pluripotent stem (iPS) cells, a small molecule ATM inhibitor decreased mutant HTT-induced cell death compared with vehicle, without affecting the viability of non-mutant cells. Next steps include selecting ATM inhibitors with good pharmacokinetic properties and blood-brain barrier penetration to test in mouse models of HD...