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Development and validation of a technological platform, through high-throughput in vivo assays on Zebrafish (Danio rerio), to test molecules (lead, hits and off-label) with therapeutic potential for cardiovascular diseases


Cardiovascular diseases (CVD) are the leaders in mortality in Brazil, with about 14 million Brazilians having some vascular or heart disease, contributing with about 30% of all deaths in the country. There are about a thousand deaths per day, numbers that are also associated with the Covid-19 pandemic, showing that this is a matter of absolute relevance to public health. Another aspect, in addition to humans, CVDs are also common in pets, especially dogs and cats, accounting for 20% of deaths. In this way, CVDs are in evidence in large economic groups that move billions of reais and boost the drug industry and its investments in Research, Development and Innovation (RD&I), in the order of US$ 133 billion in 2021, aiming at the elaboration of new drugs and biomolecules to be made available on the market, focusing on the prevention and treatment of CVD. In addition, it is important to point out that the process of discovery and development of new drugs, in addition to being complex, long and expensive, often does not pass to the next phase of preclinical tests due to side effects on the cardiovascular system, which can go unnoticed in higher-throughput studies, and are extremely valuable results to be identified before advanced-stage mammalian studies. Therefore, it is extremely important to develop modern planning strategies, standardized, validated, and high-quality trials that are based on efficacy, effectiveness and cost-effectiveness, and especially on knowledge of the pathophysiology of cardiovascular diseases. In this context, the use of Zebrafish (Danio rerio) has expanded from basic science to industry, being of particular interest for studies of new biomolecules, since Zebrafish (ZF) is able to provide a complete and integrated view of the cardiac physiology, which is currently not possible in cell culture. The high fecundity, 70% similarity to the human genome, small size and easy handling make ZF a strong candidate to offer a reliable and low-cost alternative to replace larger rodents and mammals for the study of CVD. The practicality and efficiency of this animal model can accelerate the processes for the development of new molecules, with greater predictive and informative value, allowing better scalability of tests of new drugs and biomolecules in the study of CVD. The objectives to be achieved by this proposal include the development and validation of a technological platform, with high technical and predictive capacity, through high-throughput in vivo assays, high-throughput screening (HTS), in ZF, to test molecules promising (lead), substances with biological activity (hits), as well as existing drugs (off-label), candidates to become new drugs with therapeutic potential for CVD. From an entrepreneurial perspective, the project aims to create a technology-based company aimed at exploring the benefits of this platform for CVDs, and in the future, for other chronic degenerative diseases, supporting the pharmaceutical industries in their RD&I routines, as well as Startups and other companies in the health area, which seek economy, agility, improvement and quality in the evaluation of the effectiveness of compounds of interest to human and animal health. (AU)

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