Regulating autophagy
Publication number: WO/2008/122038.
Publication date: 09.10.2008. Applicants: President and Fellows of Harvard College, Dana Farber Cancer Institute, Cambridge Enterprise Ltd., James Elliot Bradner, John Paul Shen, Ethan Oren Perlstein, David Rubinsztein, Sovan Sarkar, Stuart L. Schreiber. Inventors: James Elliot Bradner, John Paul Shen, Ethan Oren Perlstein, David Rubinsztein, Sovan Sarkar, Stuart L. Schreiber. Description: Autophagy is a cellular process by which cells canabalize non-essential cellular elements such as organelles to generate metabolites, or in some cases, to cause cell death. The present invention provides modulators of autophagy, which have been identified using a high-throughput phenotypic screen of over 3500 compounds. These modulators are useful in treating diseases ranging from proliferative diseases to neurodegenerative diseases to infectious diseases to protein misfolding states. Furthermore, the invention provides the treatment of proliferative disease such as cancer with a combination of autophagy inhibitors and protein kinase inhibitors. Details: Complete details in World Intellectual Property Organisation and European Patent Office. |
cAMP dependent induction of autophagy
Publication number: WO/2008/099175.
Publication date: 21.08.2008. Applicants: Cambridge Enterprise Ltd., David Rubinsztein, Sovan Sarkar, Andrea Williams. Inventors: David Rubinsztein, Sovan Sarkar, Andrea Williams. Description: The present invention relates to the induction of autophagy via mTOR independent pathways which modulate intracytosolic cAMP levels. In some embodiments, autophagy may be induced in a cell by reducing intracytosolic cAMP levels, for example using a cAMP antagonist, such as clonidine. This may be useful, for example in the treatment of neurodegenerative disorders or pathogen infections. Details: Complete details in World Intellectual Property Organisation and European Patent Office. |
Modulation of autophagy by calpain inhibition
Publication number: WO/2007/003941.
Publication date: 11.01.2007. Applicants: Cambridge Enterprise Ltd., David Rubinsztein, Sovan Sarkar, Andrea Williams, Evangelia Ttofi, Cahir O'Kane, Andres Floto. Inventors: David Rubinsztein, Sovan Sarkar, Andrea Williams, Evangelia Ttofi, Cahir O'Kane, Andres Floto. Description: The present invention relates to finding that the inhibition of calpain induces autophagy in eukaryotic cells through an mTOR independent pathway. Methods and materials are provided for the treatment of diseases which are ameliorated by the induction of autophagy by inhibiting calpain such as neurodegenerative and infections diseases. Also provided are screening methods for identifying compounds which inhibit calpain and may be useful for treating such conditions. Details: Complete details in World Intellectual Property Organisation and European Patent Office. |
Methods of autophagy induction in mammalian cells
Publication number: WO/2006/079792.
Publication date: 03.08.2006. Applicants: Cambridge Enterprise Ltd., David Rubinsztein, Sovan Sarkar. Inventors: David Rubinsztein, Sovan Sarkar. Description: This invention relates to the induction of autophagy in cells through inhibition of inositol monophosphatase (IMPase) and reduction in the level of free inositol (IP3). This may, for example, be useful in the treatment of a range of conditions, including neurodegenerative disorders and bacterial infections such as tuberculosis. Therapeutic compounds, uses and methods of treatment are provided, along with methods of screening for autophagy inducers. Details: Complete details in World Intellectual Property Organisation and European Patent Office. |