Study of the oxidative stress pathway and mitochondrial dysfunction in FXTAS patients. Searching for a specific biomarker that allows presymptomatic diagnosis and prognosis of the disease.

Fragile-X -Associated Tremor/Ataxia Syndrome (FXTAS) is a rare neurodegenerative disease with a reduced penetrance. Several evidences show that mitochondria play a central role in late-onset neurodegenerative diseases. Somatic mutations in mtDNA, acquired during the life-time, might contribute to physiological decline and lead to neurodegeneration that would be increased with age. The results obtained in a previous project show a deregulation of the oxidative phosphorylation pathway in FXTAS patients, in which 42 genes belonging to different complexes of the respiratory chain are affected and suggesting a possible involvement of mitochondria in the development of FXTAS. The main objective of the present project is to evaluate the mitochondrial dysfunction and the oxidative stress in 25 FXTAS patients and in 25 controls individuals (in blood and in fibroblasts cultures) and to correlate this data with clinical and molecular parameters that have already been collected. In order to achieve this goal, the mitochondrial activity, the oxidative stress level, as well as the accumulation of somatic mtDNA mutations, the copy number of mtDNA and the content of mitochondria will be assessed. These results could lead to the description of a FXTAS biomarker that will allow a better genetic counselling, a presymptomatic diagnosis as well as an early treatment of FXTAS patients and to slow down the disease progression. Furthermore, these results might open a new research line focused on the development of targeted therapies.