US 2003/0113263 A1 · Methods and reagents for using mammalian melanocortin receptor antagonists to treat cachexia

Abstract

The present invention provides recombinant expression constructs comprising nucleic acid encoding mammalian melanocortin receptors, in particular MC-4 melanocortin receptor, and mammalian cells into which said recombinant expression constructs have been introduced that express functional mammalian MC-4 melanocortin receptors. The invention particularly provides such genetically engineered cells expressing the human MC4-R melanocortin receptor for screening compounds for receptor agonist and antagonist activity. The invention also provides screening methods using genetically engineered cells expressing the human MC-4 melanocortin receptor to specifically detect and identify agonists and antagonists for this melanocortin receptor. Such screening methods are provided identifying compounds with MC-4 melanocortin receptor antagonist activity having the capacity to influence or modify metabolism and feeding behavior, particularly pathological feeding behavior such as illness-induced cachexia.

Claims15

Dependent claims

A method for characterizing a compound that prevents, inhibits or ameliorates cachexia in an animal, the method comprising the steps of:

(a) administering the compound to an animal with cachexia;
(b) comparing energy metabolism, food intake or motor activity in said animal with energy metabolism, lean body mass, food intake or motor activity in an animal with cachexia that is not administered the compound;
and
(c) identifying compounds that prevent, inhibit or ameliorate cachexia when less fat or lean body mass loss or reduction in energy metabolism, food intake or motor activity is detected in animals to which the compound has been administered than in animals to which the compound has not been administered.

1 more element

A method for characterizing a compound that prevents, inhibits or ameliorates cachexia in an animal and that is an antagonist of a mammalian MC4-R melanocortin receptor, the method comprising the steps of:

(a) providing a mammalian cell comprising a recombinant expression construct encoding a mammalian melanocortin receptor that is the MC-4 melanocortin receptor, wherein the mammalian cell expresses the melanocortin receptor encoded by the recombinant expression construct, or cell membranes prepared therefrom;
(b) contacting the cells or membranes prepared therefrom with an amount of an MC-4 melanocortin receptor agonist sufficient to produce a detectable amount of a metabolite produced in the cells that bind the agonist, in the presence and absence of a test compound to be characterized as an antagonist of the MC-4 melanocortin receptor;
(c) assaying the cells or membranes prepared therefrom for agonist binding or for the metabolite produced in cells that bind an MC-4 melanocortin receptor agonist;
(d) comparing agonist binding or metabolite production in the cells in the presence of the test compound to metabolite production in the cells in the absence of the test compound;
(e) identifying the compound as an MC-4 melanocortin receptor antagonist when less metabolite is produced in the presence of the compound than in the absence of the compound or when less agonist is bound in the presence of the compound than in the absence of the compound;
(f) administering the compound to an animal that expresses MC-4 receptor and in which cachexia is experimentally induced;
(g) comparing energy metabolism, food intake or motor activity in said animal with energy metabolism, lean body mass, food intake or motor activity in an animal in which cachexia is experimentally induced and to which the compound is not administered;
and
(h) identifying the compound as an MC-4 melanocortin receptor that prevents, inhibits or ameliorates cachexia when less fat or lean body mass loss or reduction in energy metabolism, food intake or motor activity is detected in animals to which the compound has been administered than in animals to which the compound has not been administered.

6 more elements

Dependencies are inferred from the claim text.

Methods and reagents for using mammalian melanocortin receptor antagonists to treat cachexia

Life of this patent

Methods and reagents for using mammalian melanocortin receptor antagonists to treat cachexia

Life of this patent

Abstract

Claims15