AD-9308 / Foresee Pharma - LARVOL DELTA

Aldehyde dehydrogenase 2 mitigates acrolein-driven ferroptosis to preserve kidney function. (PubMed, Environ Pollut) - "Pharmacological inhibition with ferrostatin-1, deferoxamine, or the mitochondrial ROS scavenger MitoTempo mitigated these effects, confirming the involvement of ferroptosis and mitochondrial oxidative stress. In vivo, oral AD-9308 treatment significantly alleviated acrolein-induced kidney injury in Aldh2*2 mutant mice by reducing tubular damage, fibrosis, and inflammation. Collectively, these findings identify ferroptosis as a central mechanism of acrolein nephrotoxicity and highlight ALDH2 activation as a promising therapeutic approach, particularly for individuals carrying the Glu504Lys mutation."

Journal • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Renal Disease • ALDH2

Deciphering endothelial aldehyde dehydrogenase 2, oxidative stress, and interleukin-6 interactions in pulmonary hypertension: Implications for precision medicine. (PubMed, Biochem Pharmacol) - "Moreover, these effects were mitigated by AD-9308, a prodrug of AD-5591...This study highlights the role of endothelial ALDH2 dysfunction and 4-HNE accumulation in pulmonary arterial (PA) remodeling via the p38/NF-κB/IL-6 pathway. Our findings suggest that ALDH2 enhancers may represent a promising precision medicine approach for PH management, particularly in patients with ALDH2 deficiency."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ALDH2 • FGF2 • IL6

4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification. (PubMed, Eur Heart J) - "4-HNE inhibition of Dicer directly impairs miRNA biogenesis in heart failure. Strikingly, decreasing cardiac 4-HNE levels through pharmacological ALDH2 activation is sufficient to re-establish Dicer activity and miRNA biogenesis; thereby representing potential treatment for patients with heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • ALDH2