Methods and compositions for detecting the activation of mtor pathway

The present invention relates to a method for measuring the activation of mTOR pathway in a subject suffering from a kidney disease associated with a dysregulation of the mTOR pathway comprising the following steps: i) Obtaining urine sample from said subject; ii) Detecting whether of one or more of the following members of AKT, mTOR, 4E-BP1/2 or PI3K pathway are phosphorylated in urine sample and iii) Concluding that the pathway of mTOR is activated when the phosphorylation of AKT, mTOR, 4E-BP1/2 or PI3K is detected or concluding that the pathway of mTOR is not activated when phosphorylation of AKT, mTOR, 4E-BP1/2 or PI3K is not detected. Inventors have found that patients that responded to everolimus as demonstrated by a decrease in the volume of the angiomyolipoma using MRI (patients 1 to 3), had a reduction in the phosphorylation of S6RP. On the other hand, patients with stable disease on MRI had similar amount of phosphorylation of S6RP (patients 4 to 5). Of course, in all these patients, urines were sterile without leucocyturia. They concluded that P-S6RP can be used as a biomarker to monitor the impact of mTOR inhibitors in patients with kidney disease activating the mTOR pathway.

Keywords: Kidney Disease, mTOR pathway activation, PI3K pathway activation, diagnostic, mTOR inhibitor treatment, PI3K inhibitor treatment
Patent Application number: EP20 306 534.7 on 10/12/20
WO2022122889A1 on 16/06/2022

Reference:

BIO20556-D1

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Pierre MAZOT
Pierre MAZOT
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Patent filling date: 2020-12-10

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