The metabolomics revolution

Understanding the body’s metabolic profile is transforming drug discovery and personalized medicine.

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Studying an organism’s genetic makeup allows us to determine disease risk. But it’s an organism’s metabolic profile, the levels and kinds of metabolites at a given time, which offers unique insights into disease mechanisms and treatment responses. The study of metabolites and metabolism — known as metabolomics — is allowing scientists to explore interaction between genetics and the environment. The science has the potential to detect metabolites associated with disease even before symptoms become apparent. 

“By being able to detect a specific disease before it manifests, metabolomics will allow patients and physicians to take aggressive preventative action, develop personalised therapies and monitor results,” says biochemist David Wishart of the University of Alberta in Canada. 

The field is set for rapid growth as new techniques, such as metabolite imaging, and improved analytical technologies become more accessible. Wishart conducted a review of the latest research in this field, describing recent developments and emerging applications. 

Metabolomics could offer a more productive and cost-effective route to drug discovery. As Wishart explains, relatively few diseases have a strong genetic basis and genes linked to diseases may not be amenable to drug targeting. Crucially, though, “more and more metabolic biomarkers are being discovered and they are allowing the prediction, or very early diagnosis, of diseases such as diabetes, kidney disease, preeclampsia, heart disease, colon cancer and Alzheimer’s disease”.  

Metabolites are providing insights into the underlying causes of disease and revealing unexpected therapeutic targets. In some cases, there could even be a simple therapeutic solution, as levels of a particular metabolite may be corrected with dietary supplements. 

Metabolomics can also be used to detect optimal responders to a drug in clinical trials as well as to monitor adverse responses. This can help optimize clinical trials and reduce the time needed for new drugs to reach the market. 

Newborn screening tests are based on metabolomics and are one of the most successful examples of personalized medicine. Testing a blood spot taken from a baby (often referred to as the 'heel prick') for particular metabolites allows the detection of nine rare but serious diseases, such as congenital hypothyroidism and cystic fibrosis.   

Many cancers exhibit a distinct metabolic profile. Using metabolomics to characterise tumours holds great promise for the design of customised cancer therapies.  

As more sensitive technologies emerge, the identification of metabolites will continue to improve. Wishart believes the next major breakthrough will be the development of databases and software that will permit the identification of more than 10,000 metabolites in a single mass spectrometry run.

References

  1.  Wishart, D. S. Emerging applications of metabolomics in drug discovery and precision medicine. Nature Reviews Drug Discovery  (2016).| article

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