Compositions and Methods for the Treatment of Krabbe and Other Neurodegenerative Diseases

Provided are compositions and methods for the treatment of Krabbe and other neurodegenerative diseases, including storage diseases such as GMl gangliosidosis, Niemann-Pick disease, Tay-Sachs disease, Sandhoff disease, metachromatic leukodystrophy, Canavan disease, Pelizaeus-Merzbacher disease, and storage conditions facilitated by aging of lysosomal functions, which are associated with psychosine (and/or other storage material)- -mediated axonal degeneration. Compositions and methods employ (1) one or more inhibitor of a phosphotransferase activity of one or more kinase(s) such as, for example, CDK5, P38, jnk, src, CK2, PKC, GSK3a and ss; (2) one or more inhibitor of a phosphotransferase activity of one or more phosphatase(s) such as, for example, the Ser/Thr protein phosphatase PPl and Tyr protein phosphatase PP2; one or more inhibitor of a caspase/calpain activity of one or more caspases such as caspase 3 and calpains such as calpain 1 and 2; and (4) one or more inhibitor of a sodium/calcium exchange protein such as, for example, NCXl. Inhibitors include small molecules, including the GSK3ss inhibitor L803 and the NCXl inhibitor flecainide, and siRNA molecules that downmodulate cellular levels of one or more mRNA, including siRNA that are capable of downmodulating the cellular expression of PPl. Inhibitors disclosed can cross the blood-brain barrier and, thus, are available to the central nervous system (CNS) and effective in reducing psychosine-mediated axonal degeneration.

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WO 2011019763.jpg

WO 2,011,019,763


Type of Offer: Licensing

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