Oregon Health & Science University

Louisiana State University and Agricultural & Mechanical College

Ipsen Pharma S.a.s.

Imperial Innovations Limited

Imperial College Innovations Limited

Andrew A Butler

Roger D Cone

Michael Alexander Cowley

Michael DeWitt Culler

Stephen Robert Bloom

Malcolm J Low

Caroline Jane Small

Heather A Halem

Rachel Louise Batterham

Mohammad Ali Ghatei

James L Trevaskis

Malcolm James Duncan Low

Mohammad Ali Ghatel

Michael Cowley

The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as insulin resistance.

Use of melanocortins to treat insulin sensitivity

The present invention relates to peptide ligands of the melanocortin receptors, in particular the melanocortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as insulin resistance.

The expression of a mRNA encoding a putative 76 amino acid, secreted protein ('Enho1') was found to negatively correlate with fasting triglyceride and cholesterol levels. A recombinant adenovirus was used to increase the expression of Enho1 mRNA in two mouse models of obesity, KK-Aand Lep/Lepmice. Over-expression of Enho1 by adenovirus injection significantly, and reproducibly, reduced fasting triglyceride and cholesterol levels in both models. In addition, transgenic mice strains were made that over express Enho1 protein. Additionally, the expression of a key gene involved in lipogenesis (fatty acid synthase) and FAS protein levels were reduced by ENHO1 adenoviral treatment in Lep/Lepmice. Full-length ENHO1 peptide, or peptide derivatives, homologues, analogues, or mimetics thereof, delivered by oral intake, injection, subcutaneous patch, or intranasal routes, could be used as therapeutic or diagnostic agents for hypercholesterolemia, hypertriglyceridemia, insulin resistance, obesity, diabetes, and/or energy imbalance.

Methods to treat symptoms of pathophysiology related to body mass

Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering a therapeutically effective amount of PYY or an agonist thereof to the subject, thereby decreasing the calorie intake of the subject.

Modification of feeding behavior

Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering PYY or an agonist thereof and GLP-1 or an agonist thereof to the subject, simultaneously or sequentially, thereby decreasing the calorie intake of the subject.

Modification of feeding behavior using PYY and GLP-1

Screening methods of use in identifying agents that affect caloric intake, food intake, appetite, and energy expenditure are disclosed herein. These methods are used to identify agents of use in treating obesity, or that can be used to decrease the weight of a subject. These methods can also be used to identify agents of use in treating anorexia or cachexia and can be used to increase appetite and to increase the weight and lean body mass of a subject.

Method for screening for agents that affect food intake

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Baton Rouge, LA, United States of America

Andrew A Butler