Alcediag

Biocortech

Centre National De La Recherche Scientifique

Marco Polo Pharmaceuticals

Dinah Weissmann

Camille-Georges Wermuth

Paola Ciapetti

Franck Molina

Jean-Francois Pujol

Laurent Cavarec

Laurent Vincent

Jean-François Pujol

Berengere Vire

Nicolas Salvetat

Laurence Nathalie Deyon

Siem Van Der Laan

Fabrice Chimienti

John Mann

Laurence Deyon

The present invention is drawn to a method for in vitro predicting the risk for a patient to present a pathology or to identify whether a patient is at risk to develop a pathology, such as psychiatric disorder, associated to an alteration of A-to-I editing on PDE8A transcripts, from body fluids such as a blood, urine or saliva sample of said patient. The present invention also relates to kits for the implementation of the method.

RNA editing as biomarkers for mood disorders test

The present invention relates to the use of the editing profile of PDE8A pre-mRNA as a specific bio marker of ADARs activities in evolved primate, particularly in Human tissues. The present invention also relates to an in vitro method for predicting in Human an alteration of the mechanism of the ADARs catalysed pre-mRNA editing of target genes, by analysing the PDE8A pre-mRNA editing profile in a peripheral tissue sample containing cells expressing said PDE8A pre-mRNA, such as blood sample. The present invention is also directed to an in vitro method for the screening of potential therapeutic compound and to predict and assess therapeutic efficacy and/or efficiency or to diagnose potential severe brain or peripheral drug side effects implementing said PDE8A pre-mRNA editing profile as specific biomarker. The present invention is further directed to a method for determining the PDE8A pre-mRNA editing profile in Human, particularly by capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) method after amplification by a nested PCR. Finally the invention relates to particular nucleic acid primers implemented in said nested PCR and kit comprising such sets of primers and human cells capable of expressing PDE8A and ADARs.

Editing profiling of PDE8A pre-mRNA: use as specific biomarker of ADARs activities in human tissues to diagnose and to predict and assess therapeutic efficacy and/or efficiency or potential drug side effects

The present invention relates to the use of the editing profile of PDE8A pre-mRNA as a specific bio marker of ADARs activities in evolved primate, particularly in Human tissues. The present invention also relates to an in vitro method for predicting in Human an alteration of the mechanism of the ADARs catalyzed pre-mRNA editing of target genes, by analyzing the PDE8A pre-mRNA editing profile in a peripheral tissue sample containing cells expressing said PDE8A pre-mRNA, such as blood sample. The present invention is also directed to an in vitro method for the screening of potential therapeutic compound and to predict and assess therapeutic efficacy and/or efficiency or to diagnose potential severe brain or peripheral drug side effects implementing said PDE8A pre-mRNA editing profile as specific biomarker. The present invention is further directed to a method for determining the PDE8A pre-mRNA editing profile in Human, particularly by capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) method after amplification by a nested PCR. Finally the invention relates to particular nucleic acid primers implemented in said nested PCR and kit comprising such sets of primers and human cells capable of expressing PDE8A and ADARs.

The present invention relates to in vitro methods for the determination of the potential toxicity of test compounds. The invention also comprises in vitro methods 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 serotonin 2C receptor (5HTR2C). Finally, the present invention is directed to the kits and tools for the implementation of these methods. The invention is of special utility in the pharmaceutical industry for analysis of the toxicity profile or the screening of compounds involved in drug development and/or in pharmaceutical compositions.

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

The invention relates to novel derivatives of 14,15-dihydro 20,21-dinoreburnamenin-14-ol, having formula (I) in which R represents a radical &#x2014;AR' wherein A represents a heteroatom and R&#x2032; represents a group selected from the group comprising linear or branched C-Calkyl radicals, C-Calkenyls, C-Calkynyls, arylalkyls; esters comprising the formula &#x2014;R&#x2014; CO&#x2014;O&#x2014;R; amides comprising the formula &#x2014;R&#x2014;CO&#x2014;NZY, wherein Y and Z together can form a cycloalkyl radical or a heterocyclic radical, optionally substituted by one or more alkyl radicals; a radical selected from the group comprising alkyl radicals, alkenyls or alkynyls, substituted by at least one amine with formula &#x2014;NZY; or one of the pharmaceutically-acceptable salts thereof, including the isomers, enantiomers and diastereoisomers thereof and mixtures thereof. The invention also relates to the use of the novel derivatives for the preparation of a pharmaceutical composition which is intended, in particular, for the treatment and/or prevention of depression, sleep-wake cycle disorders and symptomatic frontal disorders in cognitive components among humans.

Derivatives of 14.15-dihydro 20.21-dinoreburnamenin-14-ol and applications thereof

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Paris, France

Dinah Weissmann