Preventing airway mucus production by administration of EGF-R antagonists
AssigneeThe Regents of the University of California
InventorsJay A. Nadel, Kiyoshi Takeyama
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Abstract
Hypersecretion of mucus in the lungs is inhibited by the administration of an epidermal growth factor receptor (EGF-R) antagonist. The EGF-R antagonist may be in the form of a small organic molecule, an antibody, or portion of an antibody that binds to and blocks the EGF receptor. The EGF-R antagonist is preferably administered by injection in an amount sufficient to inhibit formation of goblet cells in pulmonary airways. The degranulation of goblet cells that results in airway mucus production is thereby inhibited. Assays for screening candidate agents that inhibit goblet cell proliferation are also provided.
Claims27
A method of treating hypersecretion of mucus in lungs, comprising:
- administering a therapeutically effective amount of an epidermal growth factor receptor (EGF-R) antagonist to a patient suffering from airway hypersecretion of mucus.
An in vitro method for screening candidate agents, comprising:
- (i) contacting an in vitro model of goblet cell proliferation with EGF or the functional equivalent thereof;
- (ii) subsequently contacting the in vitro model with a candidate agent;
- and
- (iii) assessing goblet cell proliferation;
- wherein a decrease in goblet cell proliferation is indicative of the agent's therapeutic potential.
An in vivo method of screening candidate agents comprising:
- (i) creating an animal model of hypersecretory pulmonary disease by including EGF-R;
- (ii) stimulating the induced EGF-R with a ligand, to produce mucin producing goblet cells;
- (iii) treating with a candidate agent;
- and
- (iv) assessing goblet cell proliferation or mucus secretion;
- wherein an inhibition of goblet cell proliferation or mucus secretion is indicative of the candidate agent's therapeutic potential.
A pharmaceutical formulation for treatment of airway mucus hypersecretion, comprising:
- a therapeutically effective amount of an epidermal growth factor receptor (EGF-R) antagonist is a dose sufficient to reduce airway mucus hypersecretion;
- and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.