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US 7,842,470 B2Granted
Method for pharmacoperones correction of GnRHR mutant protein misfolding
AssigneeOregon Health & Science University
InventorP. Michael Conn
Life of this patent
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Abstract
This application relates to methods of identifying pharmacoperone agents that can restore function to a misfolded protein, such as a misfolded protein that causes disease. Also disclosed are methods of using such pharmacoperone agents to treat a disease or disorder that results from the misfolded protein.
Claims25
An in vitro assay for identifying a pharmacoperone agent that restores function to a mutant gonadotropin-releasing hormone receptor (GnRHR) protein, comprising:
- exposing a cell expressing the mutant GnRHR protein to a test agent capable of penetrating a cell membrane;
- and
- measuring inositol phosphate (IP) production by the cell, wherein an increase in IP production by the cell expressing the mutant GnRHR protein compared to production of IP by a cell expressing the mutant GnRHR protein not exposed to the test agent indicates that the test agent is a pharmacoperone agent that restores function to the mutant GnRHR, or measuring GnRHR ligand binding and internalization by the cell expressing the mutant GnRHR protein, wherein an increase in GnRHR ligand binding and internalization by the cell expressing the mutant GnRHR protein as compared to GnRHR ligand binding and internalization by the cell expressing the mutant GnRHR protein not exposed to the test agent indicates that the test agent is a pharmacoperone agent that restores function to the mutant GnRHR, wherein the mutant GnRHR protein, prior to exposure to the test agent, does not increase IP production nor increase GnRHR ligand binding and internalization.
Dependencies are inferred from the claim text.