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 (see also the "Target of the Month" section of this edition of TherapeuticAdvances). Ghrelin represents one of the most promising breaking targets in the field of obesity (click here to access our recent dossier "Ghrelin: The future of obesity therapeutics?"). 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. The proof of concept for targeting ghrelin has recently received a further boost by researchers who have shown that eating dramatically reduces ghrelin levels in lean but not obese individuals. Given the orexigenic properties of ghrelin, important satiety signals appear to be absent in obesity. The effect of ghrelin blockade on food intake in obese patients remains to be seen and data is eagerly awaited.

Adapted from English et al, J Clin Endocrinol Metab 2002 Jun;87(6):2984

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk