Resolution Pharmacology- Innovative therapeutic approaches based on the biology of resolution to control chronic diseases of western societies.

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Background

Problem. There is broad recognition that evidence-based interventions have transformed cardiovascular, inflammation and endocrine care but that new therapies are still needed for growing numbers of patients with unmet need. Recent analyses remind us that the pipeline for new therapeutic agents is particularly limited (especially in cardiovascular) and the pharmaceutical industry acknowledges the need for target confidence building and pay or acceptance of cost as key barriers to translation into the distinct national Health Systems. It is estimated that only 1/1,000 of compounds entering preclinical testing are then trialed in man and the actual cost of developing a new therapeutic into clinical practice has grown exponentially over the past two decades (estimated $1.2B). Hence, there is a limited number of novel therapeutics that have been introduced in the last decades, and this paucity of success contrasts with the heavier and growing burden upon western societies by the ‘epidemic’ diffusion of pathologies and morbidities which are little understood in their aetiology and poorly managed clinically. Examples are diabetes, obesity-related disorders, hypertension and atherosclerosis, all of which contribute to the high occurrence of both myocardial infarct and stroke to name just a few-all phenomena that are also linked to the so-called ‘metabolic syndrome’. Every year, an estimated 17 million people globally die of cardiovascular diseases, particularly heart attacks and strokes. Cardiovascular diseases occur almost equally in men and women and it is the leading cause of death and morbidity worldwide.

Answer. The vast majority of current drugs have been developed by assessing their ability to block or inhibit specific biological pathways. We also note how ‘inflammatory mechanisms’ have become central to several diseases, not only those classically associated with inflammation like arthritis or vasculatides, but also cardiovascular pathologies (atherosclerosis, myocarditis), cancer, metabolic diseases and more.
Over the last 20 years or more, scientists have appreciated the biology of the resolution of inflammation, that provides a new paradigm in our understanding of the inflammatory process with the appreciation of genetic, molecular and cellular mechanisms that are engaged to actively resolve inflammation. The ‘resolution of acute inflammation’ is enabled by counter-regulatory checkpoints to terminate the host reaction while at the same time promoting healing and repair.

Future. Current medicines for the clinical management of inflammatory diseases act by blocking specific enzymes or antagonising specific receptors or blocking their ligands. We propose time is ready to exploit the concepts of resolution and use its targets and mediators for the identification of better drugs to establish ‘Resolution Pharmacology’. We predict Resolution Pharmacology will represent an important innovation in the way common diseases will be treated in the next decades of this millennium.

Scope. A series of articles on current strategies to develop and/or implement resolution pharmacology using the creativity associated with it, hence new agonists, new modes to activate pro-resolving targets, natural and/or synthetic vesicle-based therapies. Deliverables. A cutting-edge list of scholar articles to witness the birth of Resolution Pharmacology.

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