Means and methods to treat dystonia
AssigneesVib Vzw, Katholieke Universiteit Leuven, K.U.Leuven R&D
InventorsRose Goodchild, Micheline Grillet
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Abstract
The present application relates to the field of neurological diseases, particularly to dystonia, even more particularly to primary dystonia, most particularly DYT1 primary dystonia. It is disclosed that the DYT1 dystonia causative mutation in TORSIN1A leads to hyperactivation of LIPIN. The invention provides substances modulating LIPIN function, in particular RNA molecules inhibiting LIPIN function and medical uses of these LIPIN inhibitors. Methods are disclosed to screen for medicaments that counteract the effects of TORSIN1A mutation.
Claims12
A pharmaceutical composition comprising an inhibitor of functional expression of LIPIN, wherein the inhibitor is selected from a gapmer, a shRNA, a siRNA, a CRISPR-Cas, a CRISPR-C2c2, a TALEN, a Zinc-finger nuclease, an antisense oligomer, a miRNA, a morpholino, a locked nucleic acid, a peptide nucleic acid, ribozyme or a meganuclease.
-4. (canceled)
A method of screening for an inhibitor of functional expression of LIPIN, the method comprising:
- determining the storage lipid levels of Torsin knock-out cells in an in vitro cell culture;
- administering a test compound to the Torsin knock-out cells;
- and
- determining the storage lipid levels of the Torsin knock-out cells are reduced by at least 10% after administration of the test compound as compared to identical control cells to which the test compound was not administered.
A method of screening for a compound for use in the treatment of dystonia, the method comprising:
- determining the storage lipid levels and/or cell size of Torsin knock-out cells in an in vitro cell culture;
- administering a test compound to the Torsin knock-out cells;
- determining the storage lipid levels are reduced by at least 10% and/or the cell size is increase by at least 10% of the Torsin knock-out cells after administration of the test compound as compared to identical control cells to which the test compound was not administered.
A method of screening for a compound for use in the treatment of dystonia, comprising:
- expressing a human hyperactivated LIPIN1 in yeast;
- administering a test compound to the yeast;
- determining the growth of the yeast is increased by at least 10% after administration of the test compound as compared to identical control yeast to which the test compound was not administered.
(canceled)
A method for the treatment of a neurological disease in a subject, the method comprising:
- administering to the subject an inhibitor of functional expression of LIPIN;
- wherein the inhibitor is selected from a gapmer, a shRNA, a siRNA, a CRISPR-Cas, a CRISPR-C2c2, a TALEN, a Zinc-finger nuclease, an antisense oligomer, a miRNA, a morpholino, a locked nucleic acid, a peptide nucleic acid, ribozyme or a meganuclease.
Dependencies are inferred from the claim text.