A second dossier that LeadDiscovery
has recently published focuses on ghrelin, the rising star in obesity
therapeutics (click
here!). 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. Although scientists only identified ghrelin in
1999, more than 200 papers on the substance have already been published.
Ghrelin acts to stimulate food intake and once lean individual start
eating ghrelin level drop again. Thus it is believed that ghrelin acts as
a trigger to start. In the current edition of TherapeuticAdvances
we report on data showing that ghrelin levels do not fall after eating in
obese individuals suggesting that this trigger is not reset.
In contrast to ghrelin, leptin inhibits food intake and
has also been under the obesity spotlight. A leptin agonist has recently
been shown to not only reduce body weight and glucose levels in obese
animals but also to increase insulin sensitivity. Despite the promise that
leptin agonists may have for the treatment of both diabetes and obesity,
such molecules have only met with limited success in clinical trials. This
may be because the movement of leptin across the blood-brain barrier is
defective in obese patients. Protein tyrosine phosphatase 1B, which is
increased in obese individuals, is able to down-regulate leptin signaling
and offers a further explanation for the ineffectiveness of leptin
agonists in the clinic (see "Target of the Month" in the current
edition of TherapeuticAdvances).
Recent research therefore offers renewed hope that the therapeutic
potential of leptin may be exploited. Moreover, advances in our
understanding of leptin have also expanded the list of indications related
to modulation of leptin signaling. In particular, as described in TherapeuticAdvances,
leptin has now been implicated in sepsis, osteoporosis, cancer, arthritis,
multiple sclerosis and IBD.
A third obesity-related target to be featured the
current edition of TherapeuticAdvances
is interleukin-15 (IL-15). This cytokine although more traditionally
associated with inflammation has been receiving growing interest in
relation to metabolic diseases. IL-15 inhibits adipogenesis, lipid
deposition, and PPAR gamma2 expression, and, in vivo it decreases
white adipose tissue mass. Administration of IL-15 to tumor-bearing rats
also inhibits muscle wasting (cachexia), a condition that not only
severely decreases the quality of life in cancer patients but also those
with viral infections. The leaders of the IL-15/metabolic disease field
have a number of license options and these deserve further assessment.
Dossier highlights:
- 9,000 words (approx)
- Overview of clinical characteristics and current treatments of
obesity
- Overview of the development of ghrelin research and proof of concept
for it use in the treatment of obesity
- Market valuation and incidence
- Overviews of current pharmacological targets for obesity (5HT1C
agonists; beta 3 adrenoreceptor agonists; Leptin agonists; Lipase
inhibitors; Melanocortin 4 agonists)
- Profiles on 17 drugs in development or on the market from these drug
classes
- Identification of development activity surrounding ghrelin-like
pharmaceuticals
- Identification of key patents relating to the use of ghrelin-like
pharmaceuticals in the treatment of obesity
- Identification of industrial field leaders
- Strategic Analysis: Comparison of ghrelin-like pharmaceuticals to
other classes in development for obesity; suggested development steps
- Screening tools
- Field experts
- Price $350
- Published June 2002
To order - Ghrelin:
The future of obesity therapeutics? - click
here!
