A Novel Pharmacological Pathway which Destabilizes Lysosomes and Targets Oncogenic Or Other Aberrant Proteins for Destruction

Lysosomes are acidic organelles that contain hydrolytic enzymes (such as proteases) that are required for maintaining normal cellular physiology. Lysosomal enzymes participate in diverse cellular functions from degradation of endogenous abnormal or normal proteins to activation or regulation of essential cellular processes. Interfering with lysosomal function can lead to cell death as found in the case of treatment of malarial parasites. The rise in pH of acidic food vacuoles (lysosomes in eukaryotics) by a known lysosomal targeting, anti-malarial drug chloroquine (CQ), leads to death of these parasites. In vitro studies using an acute promyelocytic leukemia (APL) cell line indicate that CQ and another lysosomal targeting agent caused these leukemic cells to undergo apoptosis (programmed cell death).

Preliminary studies, performed by Dartmouth’s scholars using cultured APL cells and a mouse transplantable transgenic APL model, provided data implicating lysosomes as a molecular therapeutic target. Notably, in vivo studies using treatment with the lysosomal targeting agent CQ, delayed onset of APL in this mouse model for this leukemia. These in vitro and in vivo data indicate that lysosomes and lysosomal enzymes could be exploited as novel therapeutic targets in cancer and perhaps other disease states.

These findings are claimed in the published United States Patent Application No. 10/564,070. We are seeking an industrial partner to further refine and market this technology. (Ref: J246)

Type of Offer: Licensing

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