University of Pennsylvania

Other

Peter S Klein

Jian Huang

Douglas A Melton

Virginia Man-Yee Lee

Christopher J Phiel

Christina A Wilson

The present invention provides a therapeutic approach to maintain and expand HSCs in vivo using currently available medications that target GSK-3 and mTOR. The present invention also provides a system and method for the ex vivo culturing of HSCs, where an mTOR inhibitor is combined with a GSK-3 inhibitor within the culturing conditions.

In vivo and ex vivo expansion of hematopoietic stem cells with a targeted combination of clinically tested, FDA approved drugs

Provided is a novel use of therapeutic concentrations of an inhibitor of glycogen synthase kinase-3 (GSK-3), including lithium or any other GSK-3 inhibitor, to block, reduce or inhibit processing of amyloid precursor proteins to beta-amyloid (A&#x3b2;) peptides, which are now believed to be the principal cause of Alzheimer's disease, thereby providing methods useful for the prevention, inhibition or reversal of the disease. Also provided are methods of using agents that specifically target the &#x3b1; isoform of GSK-3, which is responsible for APP processing, making such selective GSK-3&#x3b1;-specific inhibitors especially useful in the treatment, prevention, and possible reversal of Alzheimer's disease. Further provided are kits and screening methods associated with the present methods.

Regulation of GSK-3&#x3b1; activity for the treatment or prevention of Alzheimer's disease

A method of identifying inhibitors of glycogen synthase kinase-3 is provided. The method comprises providing a mixture comprising GSK-3, a phosphate source, and a GSK-3 substrate, incubating the mixture in the presence or absence of a test compound, and assessing the activity of GSK-3 in the mixture. A reduction of GSK-3 activity following incubation of the mixture in the presence of the test compound is an indication that the test compound is an inhibitor of GSK-3.

Inhibitors of glycogen synthase kinase-3 and methods for identifying and using the same

By providing a product supporting base and frangible, removal indicating means securely retaining each product package on the support base, a unique tamper resistant, package assembly is attained, whereby the initial removal of each package from the base causes the frangible, removal indicating means to be irreversibly broken, bent or otherwise destroyed or deformed. In this way, no package can be removed for tampering and subsequently replaced on the supporting tray without the previous removal of the product being immediately apparent. In the preferred embodiments, the frangible removal indicating means comprise a plurality of finger members or flanges which embrace the package and securely retain the package to the support base. Upon removal of the package, the frangible finger members or flanges are irreversibly broken, bent, deformed or destroyed, thereby providing consumers with immediate notice that any product associated therewith has been previously removed and replaced.

Growing community of inventors

Wynnewood, PA, United States of America

Peter S Klein