Developing tools for trial readiness in primary mitochondrial myopathies of the adulthood

In recent years, there has been a surge of interest in mitochondrial diseases (MD). However, the treatment of MD is still inadequate, despite great progress in knowledge of pathophysiology and molecular genetics. There have been very few randomized controlled clinical trials for the treatment of MD. Those that have been performed were short, and involved fewer than twenty study participants with heterogeneous phenotypes. Small patient populations represent the major impediment to progress in research and care. A patient register, in combination with a biomaterial bank, can overcome this limitation. Granted by Telethon-UILDM in 2009 (GUP09004), the nation-wide Italian collaborative network has been established, and it has already developed a web-based registry of patients with MD (https://mitochondrialdisease.it). We have collected 1400 patients, with onset of the disease in both adulthood and in childhood. Besides a low prevalence there are other major limitations specific of MD. These include the lack of shared outcome measures, of useful biomarkers and the incomplete understanding of the natural history, limiting the correct interpretation, reproducibility and comparability of clinical trials in patients with MD. New therapeutic strategies have recently been emerging, some of which have shown potential efficacy at the pre-clinical level. Therefore, the establishment of means for “clinical readiness” for the development of forthcoming clinical trials is strongly needed. For these reason, aims of this project are: - Focus our efforts on primary mitochondrial myopathies with adulthood (>16-yrs of age) onset - Development and validation of shared functional outcome measures - Evaluation of new promising biomarkers, in particular FGF-21 and GDF-15. - Characterization of the natural history of selected mitochondrial syndromes with muscular involvement. These steps, fundamental to monitor in vivo the evolution of the disease and finally to have a good toolkit for future clinical trials in MD.