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iScience | September 2020

Authors: Michael J. Hamill, Raffi Afeyan, Manu V. Chakravarthy, Tony Tramontin

INTRODUCTION: Multifactorial disease pathophysiology is complex and incompletely addressed via existing targeted pharmacotherapies. Amino acids (AAs) and related metabolites and precursors are a class of endogenous metabolic modulators (EMMs) that have diverse biological functions and, thus, have been explored for decades as potential multifactorial disease treatments. Here, we review the literature on this class of EMMs in disease treatment, with a focus on the emerging clinical studies on AAs and related metabolites and precursors as single- and combination-agents targeted to a single biology. These clinical research insights, in addition to increasing understanding of disease metabolic profiles and combinatorial therapeutic design principles, highlight an opportunity to develop EMM compositions with AAs and related metabolites and precursors to target multifactorial disease biology. EMM compositions are uniquely designed to enable a comprehensive approach, with potential to simultaneously and safely target pathways underlying multifactorial diseases and to regulate biological processes that promote overall health.