A step forward in disease modelling for mitochondrial diseases

In vitro disease modelling has been always challenging, particularly so for multifactorial or late onset conditions, and for diseases affecting cell types that may be very hard to obtain and to keep in culture (such as for instance dopaminergic neurons in the case of Parkinson’s disease). In multifactorial disease, the cellular models must be characterized by the complete set of mutations defining the disorder, and possibly kept in culture for a very long time to be able to observe the phenotype of late-onset conditions (1). In this sense, the discovery of human pluripotent stem cell (PSC), with their capacity to become any cell type of the adult body, has given a new impulse to the field of disease modelling (2). By now, numerous diseases have been in vitro modelled with embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC) derivatives, with promising results (3). For instance, spinal muscular atrophy has been studied using iPSC-derived motor neurons, and the disease corrected by treatment with anti-apoptotic factors (4) and through gene editing (5). In Huntigton’s disease, the inhibition of excessive mitochondrial fragmentation in iPSC-derived neurons could rescue defects in the mutant cells (6), and in amyotrophic lateral sclerosis, the pathogenic mechanisms were described thanks to the observations made on SOD1-mutated iPSC-based cellular models (7).