Stem cell-driven drug discovery of OXPHOS diseases

Alessandro Prigione Targeting-Mitochondria-2019 updatedThe Scientific Committee of WMS is honored to announce that Dr. Alessandro Prigione, Independent Team Leader, at the Max Delbrueck Center for Molecular Medicine, Germany, will be joining us for our 10th Anniversary Edition of Targeting Mitochondria World Congress, which will be held in Berlin on October 28th-29th, 2019.

In his presentation entitled "Stem cell-driven drug discovery of OXPHOS diseases", Dr. Prigione will discuss Mutations in the mitochondrial complex IV assembly factor SURF1, representing a major cause of Leigh syndrome (LS), a rare fatal neurological disorder. SURF1-deficient animals have failed to recapitulate the neuronal pathology of LS, hindering our understanding of the disease mechanisms. We generated induced pluripotent stem cells from LS patients carrying homozygous SURF1 mutations (SURF1 iPS) and performed biallelic correction via CRISPR/Cas9. In contrast to corrected cells, SURF1 iPS showed impaired neuronal differentiation. Aberrant bioenergetics in SURF1 iPS occurred already in neural progenitor cells (NPCs), disrupting their neurogenic potency. Cerebral organoids from SURF1 iPS were smaller and recapitulated the neurogenesis defects. Our data imply that SURF1 mutations cause a failure in the development of maturing neurons. Using NPC function as an interventional target, we identified SURF1 gene augmentation as a potential strategy for restoring neurogenesis in LS patients carrying SURF1 mutations.     

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