KH176: A NEW SMALL MOLECULE TO POTENTIALLY COMBAT MITOCHONDRIAL DISEASES

Mitochondria, subcellular organelles present in virtually all cells of the body, are vital for numerous cellular processes including energy production. Failure in mitochondrial functions can originate from gene defects in the mitochondrial or the nuclear genomes leading to progressive, often early fatal, multi-system disorders (inherited mitochondrial diseases) for which there is no effective treatment (1). Khondrion is a Dutch biotech company with the mission to develop clinical relevant treatments to combat mitochondrial diseases. A common feature of mitochondrial patients is an imbalance cellular redox status (2), hence one of Khondrion's R&D projects focuses on the discovery and optimization of small molecules with antioxidant/redox regulating properties. Out of 250 newly developed chemical entities, KH176 has been selected as the lead molecule (3). KH176 proves to be an effective antioxidant and redox modulator in primary cell models of patients with different mitochondrial diseases. Moreover, it can ameliorate the severe phenotype of a mitochondrial disease mouse model, providing altogether the basis for the granting of the Orphan Drug Designation by the EMA and FDA. A phase I clinical trial is ongoing which will grant the following phases in patients and, in the end, the launching of an effective treatment for mitochondrial patients.