Next-generation metabolomics may pave way for creating new antidepressants

Depression is one of the most common diseases that affects at least 4.4% of the world population since 2015. Current antidepressants are limited by their undesirable side effects and slow onset. The development of drugs for depression is particularly challenging due to the complexity of the symptoms, heterogeneity and comorbid diagnosis. Indeed, only one new drug was approved for the treatment of depression by the US FDA in the last 10 years (2008-2018). More efforts are urgently needed to enhance the productivity and creativity of the discovery and development (R&D) of new antidepressants.

The origins of metabolomics can be traced back to the newborn screening of inborn errors of metabolism in clinical chemistry since the 1960s, which was much earlier than genomics and proteomics. With the advancements of separation and mass spectrometry detection techniques, metabolomics is entering into a new era in which researchers can gain more insights about metabolic pathways and their significance in health and disease.

Dr. Kefeng Li from the University of California, San Diego, (UCSD, San Diego, CA, USA) has been working in the field of metabolomics for years. In this paper, he and the colleagues summarized the analytical platforms for NGM and its main applications in antidepressants R&D. These platforms provide broad coverage of different classes of metabolites, superior detection sensitivity, high resolution and mass accuracy. Because of these advantages, NGM has demonstrated great potential in all the stages of pharmaceutical R&D.

Dr. Li, the corresponding author of the paper comments, "We specifically selected albiflorin, a botanical medicine isolated from Peony to demonstrate the practical utility of NGM". Natural products tend to have multiple targets and unpredictable toxicity. NGM analysis showed the potential antidepressant targets of albiflorin. NGM also confirmed the low toxicity of albiflorin. It might need over 5 years of work using traditional approaches to come up with the same conclusion that only needs 1-2 years for NGM. NMG really speeds up the development of albiflorin as a new class of antidepressant. Dr. Li adds, "Albiflorin is a very promising multi-target drug candidate with a low toxic profile, which overcomes the side effects of some of the current commonly used antidepressants".

In regarding to the future of NGM, Dr. Li underlines that "The bottlenecks of metabolomics have still not been completely solved. Standardization of metabolomic procedures and understanding the biology behind metabolomic big data are required to be further studied."