Treatment of cns disorders associated with mutations in...

A - Human Necessities – 61 – K

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A61K 31/445 (2006.01) A61P 25/16 (2006.01) C12Q 1/34 (2006.01) C12Q 1/68 (2006.01) C12N 9/24 (2006.01)

Patent

CA 2611011

Described is a method for treating an individual having a neurological disorder with an associated mutation or mutations in a gene encoding a lysosomal enzyme. Specifically, the individual is administered a specific pharmacological chaperone for the lysosomal enzyme which increases trafficking of the protein from the ER to the lysosome in neural cells, with or without concomitantly increasing enzyme activity in neural cells. Restoration of trafficking relieves cell stress and other toxicities associated with accumulation of mutant proteins. Restoration of enzyme activity relieves substrate accumulation and pathologies associated with lipid accumulation. In a specific embodiment, the neurological disorder is Parkinson's disease or parkinsonism which is associated with mutations in glucocerebrosidase.

L'invention concerne une méthode de traitement d'un individu présentant un trouble neurologique associé à une ou à plusieurs mutations dans un gène codant pour une enzyme lysosomale. De manière spécifique, on administre à l'individu un chaperon pharmacologique spécifique pour l'enzyme lysosomale qui augmente le nombre de voies d'acheminement de la protéine du réticulum endoplasmique (ER) au lysosome dans des cellules neurales, et qui peut en même temps augmenter ou pas l'activité enzymatique dans des cellules neurales. La restauration des voies d'acheminement atténue le stress cellulaire et d'autres toxicités associées à l'accumulation de protéines mutantes. La restauration de l'activité enzymatique atténue l'accumulation de substrats et les pathologies associées à l'accumulation de lipides. Dans un mode de réalisation spécifique, le trouble neurologique est la maladie de Parkinson ou le parkinsonisme associé à des mutations dans la glucocérébrosidase.

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