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Feature

Ghrelin moves back into the limelight of obesity R&D

Posted on: 09 Feb 06
 Ghrelin moves back into the limelight of obesity R&D

Summary

The prevalence of obesity has increased by 61% in the US during the period 1991-2001. According to Datamonitor’s report, Obesity - commercial opportunities and therapeutic pipeline analysis 127m people were classified obese in the seven major markets in 2003. Obesity is an active area of R&D and numerous novel molecular targets are currently being evaluated. One target, ghrelin was the subject of a major target discovery report from LeadDiscovery published in 2003 Ghrelin: Pharmaceutical & Ther

The prevalence of obesity has increased by 61% in the US during the period 1991-2001. According to Datamonitor’s report, Obesity - commercial opportunities and therapeutic pipeline analysis 127m people were classified obese in the seven major markets in 2003. Even though there is an increasing awareness of obesity in response to various advertising campaigns and educational programs, the prevalence of obesity is expected to reach 94m by 2012 in the US alone.


The two leading drugs Xenical and Meridia are both associated with unpleasant side effects, poor efficacy and high costs. Therefore, there is a huge demand in this market for drugs that can address the current unmet needs.


Obesity is an active area of R&D and numerous novel molecular targets are currently being evaluated.  One target, ghrelin was the subject of a major target discovery report from LeadDiscovery published in 2003 Ghrelin: Pharmaceutical & Therapeutic Opportunities


Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor (GHSR) which has been hypothesized to play an important role in signaling energy insufficiency.  Ghrelin levels rise prior to meals and following food deprivation.  Ghrelin administration potently stimulates feeding, while GHSR antagonists blunt feeding.


At the time of our report publication it appeared that GHSR antagonists may offer considerable benefit as anorectics.  However, 3 recent loss-of-function studies threw this concept into doubt as ghrelin-knockout failed to alter body weight or food intake.


The February 9th (2006) edition of DailyUpdates highlights a recent JCI paper that pushes ghrelin back into the limelight of obesity R&D.  In this paper, Zigman and colleagues report on the effect of knocking-out the ghrelin receptor, GHSR.  This genetic modification prevented food intake in response to exogenous ghrelin.  Moreover the fat mass of mice maintained on a high fat diet was nearly half that of wild type mice.  Likewise food intake was also considerably reduced while glucose homeostasis was improved.


These data therefore resurrect the ghrelin receptor as a candidate drug discovery target.

LeadDiscovery

Last updated on: 27/08/2010 11:40:18

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