Endocrine Therapy

Obesity and related pathologies

In vivo testing

Since its discovery, ghrelin has emerged as one of the most promising targets in the field of obesity and other potential indications. Ghrelin is a natural peptidic hormone, consisting of 28 amino acids that is predominantly produced by the stomach, but also expressed in several other tissues and exerts a wide spectrum of actions.

Besides a potent growth hormone (GH)-releasing effect, ghrelin has emerged as capable of stimulating or increasing appetite. Ghrelin appears to be an important component of the energy balance control and acts on the central nervous system (CNS) to stimulate food intake. It is also established that ghrelin induces accumulation of fat tissue and its controlled reduction may be a valid therapeutic option. Ghrelin agonists and antagonists hold considerable therapeutic potential in major disease areas.

The illustration shows a typical experiment for the investigation of a ghrelin receptor antagonist on food intake in rats. Hexarelin is a reference ghrelin agonist substance which stimulates food intake when it is injected into rats. If animals received the ghrelin receptor antagonist, JMV 2760, 15 minutes prior to hexarelin, food intake stimulation is inhibited by 80% over a 6 hour period.

Æterna Zentaris established a research collaboration agreement with the CNRS and the Universities of Montpellier (France) and Milan (Italy) whereby new chemical entities with potential ghrelin receptor modulators properties are synthetized. Compounds with the most potent affinity for the ghrelin receptor will be investigated further in order to identify clinical development candidates. Another partnership agreement was put in place with the University of Montreal to launch a preclinical research project to identify those Æterna Zentaris molecules which antagonize the effect of ghrelin on the accumulation of fat tissue using the University of Montreal unique and innovative animal models.

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