For an overview of FP6 rare diseases projects and websites, see: http://cordis.europa.eu/lifescihealth/major/rare-diseases-projects-1.htm
Rational treatment strategies combating mitochondrial oxidative phosphorylation (OXPHOS) disorders: obtaining a detailed understanding of the clinical and pathobiological consequences of OXPHOS-disease in order to develop new treatment strategies.
Clinical assessment scales were published for both adults and children - these scales are critical for assessing the long-term prognosis and response to new therapies for patients with mitochondrial diseases.
Eight new disease-causing genes and mutations were identified. It was demonstrated that mtDNA sequence variability in human and mice determine differences in the performance of the OXPHOS system and the response to drugs. The enhanced collaboration between clinicians and basic scientists enabled patients to be screened for defects linked to newly identified genes.New technologies for diagnosis were developed, such as proof of principle for the general use of complementation in diagnostic pre-screening and Complex I mutation identification.
Various in vitro, murine and fruit fly models were studied, allowing for a better understanding of the diseases. Notably, the identification and characterization of protein components of the mammalian mitochondrial nucleoid, of new proteins involved in assembly and transport into mitochondria, and the definition of the biochemical roles of proteins in mtDNA maintenance provide novel potential therapeutic targets.
Molecules have been designed that can access mitochondria and either a) manipulate mitochondrial gene expression, or b) scavenge reactive oxygen species, which can be a major cause of damage in respiratory chain disorders. Several derivatives are being assessed with the long term intention of moving into clinical trials.