Marker metabolites can be therapeutic targets as well

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Sir

Your News & Views Q&A article 'Systems biology: metabonomics' (Nature 455, 1054–1056; 2008) highlights the importance of metabonomics in the identification of metabolites associated with disease — for example, as biological markers for disease state and susceptibility, and for monitoring response to treatment. However, metabonomics can also be useful for determining the therapeutic potential of metabolites whose levels are altered in a particular disease state.

If changing concentrations of a specific metabolite can be linked to the genesis or progression of a disease, then there may be a therapeutic advantage in restoring these to normal values. This strategy has been successful, or at least promising, in many cases. For example, several anticancer treatments exploit the antiproliferative action of ceramide, the concentration of which decreases in certain cancer types (C. P. Reynolds et al. Cancer Lett. 206, 169–180; 2004). Also, increasing the concentrations of S-nitrosothiol metabolites in the airway-lining fluid, which are lowered in patients with asthma, seems to have a protective effect in animal models (L. G. Que et al. Science 308, 1618–1621; 2005).

Metabolites have a variety of cellular functions, including acting as direct regulators of gene expression, so it is not surprising that they can also function as effectors of molecular events that contribute to disease. Those positively associated with disease causation may be rarer than those that simply result from a disease.

The human metabolome comprises thousands of endogenous molecules, many of whose functions are unknown. We believe that the concept of disease-associated metabolites as potential therapeutic agents is underexploited, in comparison with their widespread use as biological markers.

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Arakaki, A., Skolnick, J. & McDonald, J. Marker metabolites can be therapeutic targets as well. Nature 456, 443 (2008) doi:10.1038/456443c

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