Ghrelin: The future of obesity therapeutics?

It is estimated that somewhere between 34 and 61 million people in the US are obese and in much of the developing world this incidence is increasing by about 1% per year. As a general guide, obesity increases the likelihood of death from all causes by 20%, and plays a major role in the development of coronary heart disease, stroke, diabetes and gall bladder disease. Following the withdrawal of early treatments, the market for anti-obesity pharmaceuticals was reestablished in November 1997, when the FDA approved Abbott's sibutramine (Reductil/Meridia), for use in obesity, and still further in April 1999, when Roche's Xenical (orlistat) was also approved. The world obesity market has been predicted to reach $3.7 billion by 2008 with a compound annual growth rate of 21.1%. This market potential has caused pharmaceutical companies to prioritize the identification of novel anti-obesity products and consequently the number of drugs in development has risen 3-fold over the past 7 years largely due to an increase in preclinical research activities. Pharmaceutical classes receiving greatest attention include 5-HT modulating drugs; beta 3 adrenoreceptor agonists; lipase inhibitors; melanocortin 4 agonists; and leptin agonists. Leptin agonists have created a storm of interest since this mediator is able to reduce feeding however recent observations that obese individuals produce high levels of and are resistant to leptin has driven the search for alternatives.

Ghrelin represents one of the most promising breaking targets in the field of obesity. Although scientists only identified ghrelin in 1999, more than 200 papers on the substance have already been published. Ghrelin acts to stimulate food intake but plasma levels are reduced in obese patients suggesting that this mediator represents a key regulator of food intake. Field-leaders currently believe that further reduction of ghrelin activity may offer a therapeutic target and hence antagonists of ghrelin receptor binding are emerging as a pharmacological option in the treatment of obesity. Correspondingly a number of tools are now available for the screening of ghrelin receptor antagonists. Despite the potential for drug discovery, ghrelin receptor antagonists have yet to appear although the publication of a number of patents suggests that such molecules may be on the way. Considering the proof of concept supporting the development of ghrelin antagonists, the potential size of the obesity market and the relative paucity of treatments available to the clinician, now is an ideal time to invest in the development of this exciting therapeutic class.

LeadDiscovery, in collaboration with one of the global leaders in ghrelin research has produced a state of the art dossier describing why and how ghrelin should be targeted; and how ghrelin sits in the context of existing therapies and candidates in development for the treatment of obesity. In short this dossier offers a "one stop shop" for personnel involved in the selection, development and commercialization of novel obesity projects.