Chemical model of a neurodegenerative disease, method for preparation and uses of same
AssigneesCentre National De La Recherche Scientifique, Universite Paris Est Creteil Val De Marne
InventorsTHIERRY MARTENS, MICHAEL RIVARD, CELINE LAURENCE, CHRISTOPHE MORIN, SONIA LEHRI-BOUFALA, NARIMANE ZEGHBIB
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Abstract
The invention concerns the use of pyridinium furosemide or one of the derivatives, analogues, salts, metabolites, or prodrugs thereof in the preparation of a chemical model of a neurodegenerative disease, preferably Parkinson's disease. The invention also concerns the corresponding chemical model and the uses of same, in particular in screening tests for identifying drug candidates.
Claims11
A method for preparing a non-human animal model of a synucleinopathy, comprising a step of administering to a non-human animal a compound selected from the group consisting of:
- (i) furosemide pyridinium;
- and
- (ii) a compound of formula (I)
- wherein:
- R1 represents a hydrogen atom, a C1-C4 alkyl, a halogen atom, —OH, —CN, —CF3, —C(═O)NH2, —C(═O)O−, or —C(═O)O—R5 where R5 represents H or a C1-C4 alkyl,
- R2 is a hydrogen atom, a halogen atom, a C1-C4 alkyl, —OH, —CN, —C(═O)NH2, —CF3, or —C(═O)OR6 where R6 represents H or a C1-C4 alkyl,
- R3 is H, a halogen atom, a C1-C4 alkyl, —OH, —CN, —C(═O)NH2, —CF3, or —C(═O)OR7 where R7 represents H or a C1-C4 alkyl, and
- R4 represents a hydrogen atom, —OH, or —OCH3,
- or a pharmaceutically acceptable salt thereof, wherein the cell system is derived from nervous tissue or is of neuronal origin,
- and whereby the non-human animal model of a synucleinopathy is obtained.
A method for evaluating, screening, or selecting a compound for the treatment or prevention of a synucleinopathy, said method comprising:
- a) administering to a non-human animal a compound selected from the group consisting of:
- (i) furosemide pyridinium;
- and
- (ii) a compound of formula (I)
- wherein:
- R1 represents a hydrogen atom, a C1-C4 alkyl, a halogen atom, —OH, —CN,
- —CF3, —C(═O)NH2, —C(═O)O−, or —C(═O)O—R5 where R5 represents H or a C1-C4 alkyl,
- R2 is a hydrogen atom, a halogen atom, a C1-C4 alkyl, —OH, —CN, —C(═O)NH2, —CF3, or —C(═O)OR6 where R6 represents H or a C1-C4 alkyl,
- R3 is H, a halogen atom, a C1-C4 alkyl, —OH, —CN, —C(═O)NH2, —CF3, or
- —C(═O)OR7 where R7 represents H or a C1-C4 alkyl, and
- R4 represents a hydrogen atom, —OH, or —OCH3,
- or a pharmaceutically acceptable salt thereof, wherein the cell system is derived from nervous tissue or is of neuronal origin,
- b) administering to said non-human animal the test compound, and
- c) detecting or quantifying a marker characteristic of the synucleinopathy to determine the effectiveness of the test compound for reducing the marker characteristic of the synucleinopathy,
- wherein step b) may be implemented simultaneously, before, or after step a), or may overlap step a).
A kit for implementing a method for evaluating, screening, or selecting a compound intended for the treatment or prevention of a synucleinopathy, or for the preparation of a non-human model of a synucleinopathy, comprising:
- a compound selected from the group consisting of:
- (i) furosemide pyridinium;
- and
- (ii) a compound of formula (I)
- wherein:
- R1 represents a hydrogen atom, a C1-C4 alkyl, a halogen atom, —OH, —CN,
- —CF3, —C(═O)NH2, —C(═O)O−, or —C(═O)O—R5 where R5 represents H or a C1-C4 alkyl,
- R2 is a hydrogen atom, a halogen atom, a C1-C4 alkyl, —OH, —CN, —C(═O)NH2, —CF3, or —C(═O)OR6 where R6 represents H or a C1-C4 alkyl,
- R3 is H, a halogen atom, a C1-C4 alkyl, —OH, —CN, —C(═O)NH2, —CF3, or
- —C(═O)OR7 where R7 represents H or a C1-C4 alkyl, and
- R4 represents a hydrogen atom, —OH, or —OCH3,
- or a pharmaceutically acceptable salt thereof;
- and
- a non-human-animal to be administered with the compound in order to obtain said non-human model.
Dependencies are inferred from the claim text.