Evaluation of the potential risk of drug induced mood disturbance and suicide: use of a dedicated platform

An in vitro method comprising the following steps of:

• a) obtaining a biological sample containing mammal cells origin which exhibit a regular and constitutive expression of the editing enzymes ADAR1a, ADAR1b and ADAR2 and the 5-HT2C receptor;
• b) contacting said mammals cells with the compound to be tested;
• c) determining in the cellular RNA extract:
• the editing profile giving the mean proportion of each identified isoform of the 5-HT2CR mRNA measured in the cellular RNA extract, and
• the quantitative expression of said editing enzymes ADAR1a, ADAR1b and ADAR2;
• d) comparing the results obtained in step c) between said treated cells with the compound to be tested and non treated control cells, and
• e) selecting a therapeutic compound useful for the treatment of pathology related to an alternation of the mechanism of the MRNA editing of ADAR dependent A to I mRNA edition of the 5HTR2C,
• wherein in step a), said mammal cells are from the human neuroblastoma SH-SY5Y cell line.

A kit for the determination of the potential toxicity or side-effects of a test compound after its administration in a patient or for the selection of therapeutical compounds useful for the treatment of pathology related to an alteration of the mechanism of the mRNA editing of ADAR dependent A to I mRNA editing of the 5HTR2C, said kit comprising:

• a) mammal cells from a cell line wherein said cells express the editing enzymes ADAR1a, ADAR1 b and ADAR2 and the serotonin 2C receptor (5HTR2C), wherein said mammal cells are from the human neuroblastoma SH-SY5Y cell line;
• and
• b) two set of primers for measuring by a quantitative (Q) PCR involving a nested type PCR comprising two rounds of PCR each isoform of the 5-HT2CR mRNA which can be present in a RNA extract of said mammal cells;
• and
• c) a set of primers for measuring by a quantitative Q-PCR the quantitative expression of the editing enzymes ADAR1a, ADAR1 b and ADAR2.