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Sep. 1, 2013

Discovery of blood biomarker for chronic fatigue syndrome

RIKEN No.: 07785

Inventors

Yosuke Kataoka (RIKEN Cellular Function Imaging Team and Graduate School of Medicine, Osaka City University), Jin Guanghua (RIKEN Cellular Function Imaging Team), Tomoyoshi Soga (The Institute for Advanced Biosciences, Keio University)

Background

According to an epidemiological survey in Japan, about 60% of the general public has subjective symptoms of fatigue, and more than half of them suffers from chronic fatigue persisting for 6 or more months. About half of those with chronic fatigue feel deteriorated productivity in their work or study, which causes about 1200 billion yen of economic loss in total.

Some of these people are diagnosed with chronic fatigue syndrome, a medical condition whose chief complaint of severe fatigue has not been fully elucidated. About 0.2 to 0.3% of the whole population in Japan has this chronic fatigue syndrome. The mechanism of onset for chronic fatigue syndrome is not known, and currently, it is diagnosed based on patient-reported subjective symptoms and the results of physical examination by physicians. Chronic fatigue syndrome poses problems ranging from economic burden on the patients, necessity of prolonged follow-up and inconsistent diagnosis criteria among physicians.

Summary

We explored an objective biomarker for fatigue based on the mechanism of chronic fatigue, by exhaustive analysis of difference in metabolites in plasma between the patients with chronic fatigue syndrome (n=20) and healthy volunteers (n=20). No difference was observed in blood glucose (glucose level) between the groups, but it was detected that the patients with chronic fatigue syndrome had decreased metabolites in the glycolysis pathway and the TCA cycle responsible for energy production (ATP), and the level of decrease correlated with performance status (PS). We found a possibility that chronic fatigue syndrome can be objectively diagnosed with 95% accuracy based on three values of Citrate/Glucose ratio that reflects function of glycolysis pathway, Isocitrate/Citrate ratio that reflects Aconitase activity at upstream of TCA cycle, and Isocitrate/Malate ratio that reflects recovery of metabolism function at downstream of TCA cycle.

Figure comparing levels of metabolites in TCA cycle

Fig. 1: Decreased levels of metabolites in TCA cycle

Figure showing the performance Status

Fig. 2: Performance Status

Figure showing the discriminant model

Fig. 3: Discriminant model by rate of metabolites

Merits

  • Chronic fatigue syndrome can be diagnosed by measuring only several metabolites
  • Effect of treatment and course of recovery can be followed-up
  • Since these biomarkers are based on the mechanism of fatigue, they can be used for development of treatment and prevention of fatigue

Applications

  • Development of a kit for objective and rapid diagnosis of chronic fatigue syndrome
  • Development of a method to plan treatment strategy and to predict its effect, based on mathematical programming
  • Development of diet and drug that prevents/alleviates fatigue

Reference

  • 1.PCT/IB2011/001917

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