First Blood Test to Determine The Body Clock of Individuals

Time medicine has (finally) the wind in its sails. Driven by the recognition of the Nobel Prize 2,017 (for the discovery of the biological mechanisms of the circadian clock), tools are being developed at high speed to move towards a personalized chronomedicine. A Chicago team at Northwestern University offers in the "PNAS" a simple test called "TimeSignature" to determine the biological clock of each individual. This innovative approach is based on a powerful algorithm that allows it to require only two blood samples.

A standard chronotherapy today

For Prof. Francis Lévi, a pioneer in cancer timing, now coordinator of the European Inserm/Warwick associated laboratory on the personalization of chronotherapy: "Today, we know how to do group chronotherapy, for example, we know that it is better to give glucocorticoids in the morning, NSAIDs in the afternoon or evening, fluorouracil in the early night, oxaliplatin in the early afternoon or irinotecan in the very early morning. But what about subjects with altered, decoupled, out of sync, or even non-existent rhythms? This is the question that tests of this type must answer. There are already many indicators of the human body clock, such as melatonin at night or cortisol peak in the morning. But as Étienne Challet, head of the "Circadian clocks and metabolism" team at the Institute of Cellular and Integrative Neurosciences (CNRS/University of Strasbourg) explains: to have the phase of an individual, the methods are inconvenient, with repeated samples.

The mononuclear cell model

The biological clock is a multi-oscillating system, with a central clock that orchestrates the timing of peripheral clocks. The Chicago researchers used mononuclear cells called PBMC (peripheral blood mononuclear cells). "These cells have the characteristic of having a peripheral clock in phase with the main clock," explains Étienne Challet. Rosemary Braun's team has successfully developed an algorithm to determine an individual's internal time from the expression level of messenger RNA in these cells. »An interesting test but to be validated.

The Time

Signature tool is not yet proven, says Francis Lévi. "The test was developed in healthy subjects," he explains. It does not take interpatient variability, especially in sick subjects. No model does not take into account individuals who have profound destruction of the circadian rhythm. It is not known how tests of this type behave in sick subjects. »For this pioneer working on the subject for more than 30 years, the problem is one of concepts. "These molecular biology articles assume that the clock works for everyone and in the same way," he continues. However, this is not true. These new data must be converged with medical expertise and these tests must be tested prospectively in protocols. "A European project coordinated by Prof. Levi is currently testing the combination with biomarkers such as wakefulness/activity rhythm, temperature, sleep, measured continuously using sensors.