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Return to introduction on drug discovery ~ LeadDiscovery Reports Developing gene therapy approaches to target GLP-1 independently of dipeptidyl peptidase IV (DPP IV): New approaches to the treatment of diabetes GLP-1 is an endogenous hormone released
after food consumption to stimulate insulin secretion. The next wave of oral
non-insulin antidiabetic drugs set to enter the market includes GLP-1 mimics and
inhibitors of dipeptidyl peptidase IV (DPP IV), the enzyme responsible for the
breakdown of endogenous GLP-1 (see
Non-insulin Antidiabetics Three New Classes Compete for Market Control).
Researchers based in
It is estimated that there are more than 38 million people in the seven major markets with diabetes and this figure is set to rise to 50 million in 2012. However, despite this vast potential patient population, a broad spectrum of unmet needs exists and to address these new classes of oral non-insulin antidiabetic drugs are set to enter the market (see Non-insulin Antidiabetics Three New Classes Compete for Market Control). Oral antidiabetic drugs have traditionally focused on metformin
and sulphonylurea. Until 1995, the sulfonylurea class of drugs which act by
increasing insulin secretion was the only choice in the
GLP-1 is an endogenous hormone released from pancreatic alpha cells after food consumption. This hormone makes beta-cells competent and sensitizes cells from diabetic individuals to release insulin in response to elevated glucose levels. In animal studies, administration of GLP-1 agonists also resulted in preservation and formation of new beta cells which fail as type 2 diabetes progresses. This class aims to address two of the main unmet needs in diabetes treatment, prolonged efficacy and the potential to act on the underlying cause of the disease rather than on its symptoms. GLP-1 is highly susceptible to protein degradation by dipeptidyl peptidase IV (DPP IV) precluding the therapeutic potential of endogenous GLP-1 itself. Instead, GLP-1 mimetics that are resistant to degradation or DPP IV inhibitors are being developed. Exenatide, a synthetic form of exendin-4, is the lead GLP-1 mimic and was initially developed by Amylin. In September 2002 the company announced a global agreement with Eli Lilly to collaborate on the development and commercialization of exenatide. Exenatide, like GLP-1, is a peptide and although it is resistant to degradation by DPP IV it must be administered by injection. To address this issue Amylin are developing an injectable sustained release formulation of exenatide, referred to as exenatide LAR, in partnership with Alkermes. The launch of exenatide LAR is expected to lag behind that of exenatide by about two years, however its forecast revenue are massive, growing steadily to $1.5 billion by 2012. Despite the improvements afforded to exenatide LAR over
exenatide its injectable route of administration will mean that it will
inevitably be compared with insulin and analysts believe that it will probably
being reserved for later stages of therapy. Researchers in
Researchers have previously reported that transfection of insulinoma cells with a GLP-1 minigene conferred glucose sensitive GLP-1 secretory ability to these cells. Islam et al have now extended this line of research one step further. In their Life Science paper, this group based at the Karolinska Institute transfected rat insulinoma cells with a plasmid encoding GLP-1-Gly8, a form of GLP-1 resistant to DPP-IV degradation. Tranfection dramatically increased GLP-1 bioactivity in insulinoma conditioned medium and furthermore the level of insulin released by these cells in response to glucose was increased 3-fold. This likely involves a paracrine pathway since insulinoma cells express GLP-1 receptors. Although the development of gene therapeutic approaches is still in its ascendancy diabetes represents a key indication for this area of the biotechnology sector (see Cell Therapy - Technologies, Markets and Companies). Further development of GLP-1 therapeutic approaches is eagerly awaited.
Entry date
Life Sci. 2005 Jan 28;76(11):1239-48. Epub 2004 Dec 08 LeadDiscovery and BioPortfolio aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of LeadDiscovery and BioPortfolio may hold positions in some or all of the stocks discussed in this report. This abstract has been produced by LeadDiscovery Ltd. Founded by life scientists for life scientists we aim to help industry identify cutting edge drug discovery options and academic/biotech institutions maximize the potential of their research. Abstracts strictly reflect the opinion of LeadDiscovery's editorial panel. While all reasonable efforts are made to ensure the accuracy of information provided LeadDiscovery and the publisher BioPortfolio, takes no responsibility for incorrect or misleading information. LeadDiscovery is designed for educational and drug development purposes only and is not intended or designed to offer medical advice or advice of any sort, and must not be used for such purpose. The information provided through LeadDiscovery and BioPortfolio should not be used for diagnosing or treating a health problem or a disease and no reliance should be placed on any information contained in this abstract or elsewhere on LeadDiscovery's and BioPortfolio's website. It is not intended to be a substitute for professional care. If you have or suspect you may have a health problem, you should consult your physician or other health care provider. |
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