Treatment of parkinson's disease with oligonucleotides

Details Treatment of parkinson's disease with oligonucleotides Treatment of parkinson's disease with oligonucleotides

A - Human Necessities

61

K

A61K 31/7088 (2006.01) A61P 25/16 (2006.01) C12N 15/11 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2350212

The present invention relates to a method of treatment of Parkinson's disease, and to the use of antisense oligonucleotides or triplex oligonucleotides introduced into targeted brain structures to decrease the function of brain circuits known to be overactive in the Parkinsonian brain. Antisense or triplex oligonucleotides are targeted to the internal globus pallidus and/or substantia nigra pars reticulata (SNr) where the expression of glutamic acid decarboxylase (GAD67, GAD65, or a combination of the two isoforms) is downregulated. The present invention also relates to a method of treatment of Parkinson's disease where antisense or triplex oligonucleotides are targeted to the internal globus pallidus and/or substantia nigra pars reticulata for the downregulation of glutamate receptors. The present invention further relates to a method of treatment of Parkinson's disease where antisense or triplex oligonucleotides are targeted to the thatlamic motor nuclei for the downregulation of GABA receptors.

L'invention concerne un procédé de traitement de la maladie de Parkinson et l'utilisation d'oligonucléotides antisens ou d'oligonucléotides triplex introduits dans les structures ciblées du cerveau afin d'affaiblir la fonction des circuits cérébraux connus pour leur hyperactivité dans un cerveau atteint de la maladie de Parkinson. Les oligonucléotides antisens ou triplex sont dirigés sur globus pallidus interne et/ou sur substantia nigra pars reticulata (SNr) dans lesquels l'expression de décarboxylase d'acide glutamique (de GAD¿67?, de GAD¿65? ou d'une combinaison des deux isoformes) est régulée à la baisse. L'invention se rapporte aussi à un procédé de traitement de la maladie de Parkinson selon lequel les oligonucléotides antisens ou triplex sont dirigés sur globus pallidus interne et/ou sur substantia nigra pars reticulata pour réguler à la baisse les récepteurs de glutamate. La présente invention se rapporte en outre à un procédé de traitement de la maladie de Parkinson selon lequel les oligonucléotides antisens ou triplex sont dirigés sur les noyaux moteurs thalamiques des récepteurs de GABA.

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