Hamill Michael J, Afeyan Raffi, Chakravarthy Manu V, Tramontin Tony
Axcella Health Inc., Cambridge, MA 02139, USA.
Flagship Pioneering, Cambridge, MA 02139, USA.
iScience. 2020 Sep 29;23(10):101628. doi: 10.1016/j.isci.2020.101628. eCollection 2020 Oct 23.
Multifactorial disease pathophysiology is complex and incompletely addressed by 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.
多因素疾病的病理生理学很复杂,现有靶向药物疗法对此并未完全解决。氨基酸(AAs)及相关代谢产物和前体是一类内源性代谢调节剂(EMMs),具有多种生物学功能,因此,作为潜在的多因素疾病治疗方法,人们已经对其进行了数十年的探索。在此,我们综述了关于此类EMMs在疾病治疗方面的文献,重点关注有关AAs及相关代谢产物和前体作为针对单一生物学的单一药物和联合药物的新兴临床研究。这些临床研究见解,除了能增进对疾病代谢谱和联合治疗设计原则的理解外,还凸显了开发含有AAs及相关代谢产物和前体的EMM组合物以靶向多因素疾病生物学的机会。EMM组合物经过独特设计,能够采用综合方法,有可能同时安全地靶向多因素疾病的潜在途径,并调节促进整体健康的生物学过程。