MITOCHONDRIA-TARGETED THERAPY:CHALLENGES AND HURDLES OF DRUG DISCOVERY PROCESS

Abstract

Mitochondria play a central role in cell life and death. Impairment of mitochondrial functions is observed in a diversity of pathological states such as cancer, diabetes, metabolic disorders and age-related neurodegenerative diseases. The wide-ranging impact of mitochondria highlights those organelles as prime targets for drug discovery. However, the development of mitochondrial-targeted drugs has been hampered by a number of challenges, and there are, at present, no approved therapies. Classically, drug design based on one drug-one target approach has been used in drug discovery projects. However, for some time, drug discovery players have been questioning the success of the reductionist philosophy to ameliorate disease states with multifactorial and polygenic nature. Consequently, the multi-target approach, where a single chemical entity may be able to modulate simultaneously multiple targets, seems to be of particular interest. One of the main limitations with this approach is related to the ability to define the set of targets that are causative of a particular disease state and design compounds that will hit the key targets with a desirable ratio of potencies. This is certainly a daunting challenge but given the current unmet medical needs, and the advantages if the approach is successful, such a venture is worthwhile. Yet, the collaboration among all the stakeholders, like research foundations, academic institutions, physicians, and pharmaceutical industry, are paramount for the success (see COST Action CA15135).