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Pharma Focus & Mitochondria
Complex biochemical, hormonal and hemodynamic mechanisms are involved in the pathogenesis of target organ damage (TOD). Common to all these processes is an increased bioavailability of reactive oxygen species (ROS). Mitochondria play the central role in supplying cells with ATP and are also the major source of ROS - molecules of both regulatory and destructive nature. Both in vitro and in vivo studies explored the role of 
mitochondrial oxidative stress as a mechanism involved in the pathogenesis of TOD. Dysfunction of mitochondrial proteins associated with mitochondrial DNA (mtDNA) damage, and the interaction between mitochondria and other sources of ROS play an important role in the development of many diseases such as endothelial dysfunction, cardiac hypertrophy, renal and cerebral damage and cancer.
Why target mitochondria ?
 
While the mitochondrion has long fascinated biologists and the sheer diversity of druggable targets has made it attractive for potential drug development, there has been little success translatable to the clinic. Given the diversity of inborn errors of metabolism and mitochondrial diseases, mitochondrially mediated oxidative stress (myopathies, reperfusion injury, Parkinson's disease, ageing) and the consequences of disturbed energetics (circulatory shock, diabetes, cancer), the potential for meaningful gain with novel drugs targeting mitochondrial mechanisms is huge both in terms of patient quality of life and health care costs. In this themed question ICDD functions as a Contract Research Organization (CRO) taking advantage of its expertise in studying the mitochondrial function to support the early phases of product development programs in Lead Selection & Optimization as well as in the investigation of Mechanism of action for experimental compounds.
Demonstrate safety and efficacy of your compounds by innovative technologies based on mitochondrial functions in living cells.
Measure mitochondrial bioenergetic balance as an early indicator of mitochondrial liability.

Assess the toxicity profile of your leads / candidates in the predictive Cellesis toxicity profiler.
1- Rubattu S, Pagliaro B, Pierelli G, Santolamazza C, Castro SD, Mennuni S, Volpe M. Pathogenesis of Target Organ Damage in Hypertension: Role of Mitochondrial Oxidative Stress. Int J Mol Sci. 2014 Dec 31;16(1):823-839.
2- Tokarz P, Blasiak J. Role of mitochondria in carcinogenesis. Acta Biochim Pol. 2014 Dec 11. [Epub ahead of print]
3- Davidson SM, Lopaschuk GD, Spedding M, Beart PM. Mitochondrial pharmacology: energy, injury and beyond. Br J Pharmacol. 2014 Apr;171(8):1795-7.
 
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