The process of discovery and development of novel therapeutics in the context of pharmacology and drug development (one of the four Public Policies in Portugal) has several critical points which determine the ability of molecules to become promising drugs. During pre-clinical studies, it is critical to understand whether a drug candidate presents cellular and mitochondrial liabilities which may jeopardize its future use in the clinical market. Since mitochondria, the cell powerhouses, are responsible for a number of critical functions in cellular metabolism, it is logical that molecules that present toxicity for this intracellular organelle lead to cellular bioenergetic disruption with a consequent failure of the organ.
To answer an unmet need of the market, our MitoXT service platform was developed to analyze the toxicity and safety of various classes of compounds using in situ mitochondrial function as a highly reliable and precise biosensor. In this sense, difficult-access highly-specialized services support research groups or pharmaceutical/nutrition industry to assess the toxicity and safety of compounds intended for human use, including at preclinical stages of drug discovery and development. Our toxicological tests are highly reliable, enabling a timely screening of toxic compounds, in order to prevent the development of future complications and the appearance of long-term adverse reactions that limit their clinical use and lead to market withdrawal. In alternative, the MitoXT service platform has been also focused in assisting research groups or industry to validate the use of specific molecules or biological extracts as cellular or mitochondrial protective agents, in order to counteract oxidative stress or other stress agonists, thus paving the way for their therapeutic application.
We have also been involved in characterizing the mitochondrial function in cells from different origins, including patients suffering from different metabolic diseases (including mitochondrial diseases), or animal models.
Our toxicological tests provide certified analysis of mitochondrial function based on Seahorse Extracellular Flux Analyzer platform XFe96, one of the two equipments of this kind in Portugal, complemented also with other assays which provide a full picture of mitochondrial metabolism at the cellular level.
Currently, we are in the process of developing alternative toxicity testing models and techniques in order to better serve other requirements. In development are genotoxicity tests, based on FADU technique, using for this the gTOXX Analyzer platform, the only of this kind in Portugal.
Customers so far include the University of Wyoming and the Texas Health Science Center (USA), the Nencki Institute of Experimental Biology (Poland), the Institute for Biomedical Research (Spain), CEDOC, Universities of Minho and Porto (Portugal), Biocev (Czech Republic), and the start-up company mitoTAG. In the period 2015-2020, MitoXT Services raised about 80,000 Euros from different customers.
In one particular case, and clearly related with pharmacology and drug development, we have provided services to a R&D institution in Portugal which is developing novel molecules for Parkinson disease, which were designed and synthesized to have the same efficacy in the central nervous system, while having lower hepatic mitochondrial function. These molecules are now geared to enter in vivo studies and possibly enter in a licensing agreement with a large pharmaceutical company.
