DOSE-AND AND TIME-DEPENDENT EFFECTS OF TREATMENT WITH HUMAN BONE MARROW-DERIVED STROMAL CELLS IN A RAT MODEL OF SPINAL CORD INJURY

摘要: Mutations in mitochondrial complex IV assembly factor SURF1 causes Leigh syndrome (LS), a rare incurable neurodevelopmental disorder typically affecting midbrain and basal ganglia structures. SURF1-deficient animals fail to recapitulate the patient neuronal pathology, thereby hindering the discovery of treatments. We previously generated a model of LS using patient-derived induced pluripotent stem cells (iPSCs) carrying SURF1 mutations and identified impaired neuronal branching as a key pathogenetic mechanism. Here, we aimed to discover treatment strategies ameliorating the branching capacity of SURF1-mutant neuronal cells. We used singlecell transcriptomic datasets from SURF1-mutant cerebral organoids to feed a machine-learning algorithm that identified 28 druggable molecular targets affected by SURF1 mutations. We prioritized nine compounds and tested them using isogenic iPSC lines …