In Pearson syndrome (PS), there are abnormalities of the DNA inside a specific part of the cell, called the mitochondria. Mitochondria are important for many functions in each cell, and thus in the whole body, in particular energy production. Abnormalities in the mitochondrial DNA (mtDNA) are not uniform in the cells of patients with PS – some mtDNA is normal and some mtDNA is abnormal. The proportion of mtDNA that is abnormal determines the degree of dysfunction in the cell and the body. In the research funded by the Associazione Luigi Comini, we are seeking ways to restore function in cells in patients with PS. Specifically, we are developing methods to screen all the genes in the entire human genome, to see if altering one of these genes may decrease the abnormal mtDNA and / or restore function despite abnormal mtDNA, in PS patient’s cells. Under the Associazione Luigi Comini funding, we performed extensive method development to enable this powerful screening procedure. Now, we are executing the screening method, in hopes of finding new drug targets for patients with PS and other mitochondrial diseases. We are very grateful for the tremendous support of the Associazione Luigi Comini, without which this research would not be possible.