Treating induced pluripotent stem cell (iPSC)-derived motor neurons derived from ALS patients and controls with an inhibitor of DNA2, cellular viability and mitochondrial membrane potential (MMP) were mostly reduced in iPSC-derived motor neurons of controls, thus demonstrating a disease-associated compensatory increase in mtDNA-CN, which is coincident with reduced vulnerability to DNA2 inhibition (Table 4). Here, DNA2 is linked to amyotrophic lateral sclerosis.