Precise measurement of concentrations of the H6D variant of GDF15 using different assays

Summary

Protein Growth-Differentiation Factor 15 (GDF15) is a newly discovered hormone that can be produced and released into the bloodstream by any cell in the body that is undergoing stress. It acts on the brain to activate hormonal pathways that assist in survival under severe stress; it also seems to play an important role in inducing “illness behaviour” such as lying down and not feeling like eating, which probably helped humans to overcome a range of threats to our survival during our evolution. Today, its major medical significance is in a condition called cancer cachexia, where people with certain cancers lose their appetite and also develop muscle wasting. Many cancers are associated with high circulating GDF15 levels and blocking the action of GDF15 is showing early promise in clinical trials.

Clearly, accurate and precise measurement of GDF15 is critical, as this treatment will only be useful in cases where GDF15 levels are high. We have found that a common genetic variant in GDF155 (H6D) seriously interferes with its measurement by some widely used assays. We have been working with a small diagnostics company that has produced a new assay that is likely not to be interfered with by this genetic variant and in this study we wish to test whether this is the case. We will do so by using the range of available assays to measure GDF15 in 173 stored plasma samples from participants in the Cambridge BioResource whose genetic status of the DNA encoding GDF15 is already known. Having an accurate and affordable means of measuring GDF15 will help advance the development of treatments for cancer cachexia and other conditions (i.e. appetite suppression in obesity).