Research

The first pathogenic mutation in human mitochondrial DNA was identified in 1988. In less than 15 years research on mitochondrial diseases has developed rapidly and is continuously evolving. More than 100 pathogenic mutations in mitochondrial DNA have now been described. Moreover, the completion of the human genome project has been a great contribution in helping identify mutations in nuclear genes that cause mitochondrial diseases.
Through the past several years basic researchers and clinical researchers have been working together to form a “task force” to clarify the still many obscure aspects of the biology and pathology of mitochondria.

In Europe the MitEuro association, made up of 51 research laboratories including our own , and covering different branches of research, is occupied in trying to clarify the molecular, cellular and physiopathological mechanisms of mitochondrial diseases with the aim of identifying effective treatments.

Our most important research programs are:

• Studies on the molecular pathogenesis of respiratory chain disorders
  
• Characterization of nuclear genes responsible of mitochondrial disorders
  
• Characterization of genes responsible of structural abnormalities of mtDNA
  
• Epidemiological studies and systematic screen of respiratory chain disorders
  

Thanks to an intense research activity, our center has identified numerous pathologies characterized by DNA mitochondrial instability produced by mutations in specific nuclear genes. These diseases are characterized by the presence of a myopathy with ptosis and Progressive External Ophthalmoplegia (PEO) caused by the accumulation of multiple deletions in mitochondrial DNA.

The genes responsible for these disease have been recently identified, thanks to a vast European collaborative network which our center is part of. Our Center has also identified mutations in Surf I, the gene responsible for Leigh’s syndrome, a serious childhood neurodegenerative disorder associated with a specific defect of cytochrome c oxidase (complex IV of the respiratory chain). One interesting development in this research area has been the creation of an animal carrying a SURF-1 deficiency.
This animal model will be useful for the understanding of the pathogenetic mechanism and possible therapies for this severe disease. The aim of other studies is to identify and characterize new nuclear genes responsible for different pediatric mitochondrial pathologies. We are also involved in developing rapid and efficient molecular tests, by means of high-throughput instruments that will permit to automate the procedure, reduce diagnostic errors, and lower the costs.

The results that we expect from these projects will be important for both the improved diagnosis of mitochondrial diseases, offering a better service to patient and family and for the advancement of scientific knowledge of these pathologies. In turn, this information will be important for genetic counseling, pre-natal diagnosis and the study of treatment strategies.