Many investigational drugs showed promise in pre-clinical studies, including selective and reversible ALDH2 inhibitors (e.g., ANS-6637) and genetic targeting of liver ALDH2 messenger RNA to locally reduce hepatic ALDH2 expression (305, 306). However, a Phase 2 clinical study evaluating ANS-6637 in treatment-seeking adults was terminated early due to concerns of liver toxicity (307), and efficacy results for a clinical trial using a hepatic ALDH2 mRNA inhibitor (DCR-AUD) are not yet publicly available (NCT05845398). Overall, targeting ethanol metabolism offers promise but requires caution due to risks from metabolic intermediates and non-target effects, and further research is needed.
