Date: 2013-02-11
Type of information: Development agreement
Compound: novel therapies for severe obesity (positive allosteric modulators or PAMs that increase MC4-R activity)
Company: GSK (UK) Vanderbilt University (USA -TN)
Therapeutic area: Metabolic diseases - Endocrine diseases - Hormonal diseases
Type agreement: development
commercialisation
Action mechanism: Up to 5 percent of cases of severe, early-onset obesity have been linked to heterozygous mutations in MC4-R that reduce melanocortin signaling by less than 50 percent of normal levels. Clinical trials of drugs that directly activated every MC4 receptor throughout the brain were not successful, however, because some individuals experienced a rise in blood pressure. In comparison, positive allosteric modulators or PAMs act indirectly, to “boost” only those receptors that already being turned on by a native hormone. This approach should avoid raising blood pressure in patients with partially defective melanocortin signaling, and may be effective in treating common obesity.
Disease: severe obesity
Details: * On February 11, 2013, Vanderbilt University has signed a collaboration agreement with GSK for the discovery, development and commercialization of novel therapies for severe obesity. The target is the melanocortin-4 receptor (MC4-R), which is involved in energy homeostasis, the balance of food intake and energy expenditure, and in the regulation of body weight. Defective melanocortin signaling is the most common cause of severe, early-onset obesity. With major support from the National Institutes of Health (NIH), Roger Cone, Ph.D., and colleagues at Vanderbilt have identified a series of drug-like compounds, called positive allosteric modulators or PAMs, that “gently increase” MC4-R activity. The project was launched by Jacques Pantel, Ph.D., now at the French National Institute of Health and Medical Research in Paris. Postdoctoral fellow Julien Sebag, Ph.D., then led the screen with the assistance of lab manager Savannah Williams, primary research assistant for the project.
Under the collaboration agreement, Vanderbilt will do the pharmacology and pre-clinical testing, while GSK scientists will try to develop chemically similar compounds with improved activity and efficacy. The goal is to begin phase-1 testing in humans within three years — in 2016.
The agreement with Vanderbilt is the second GSK has signed with a U.S. institution under its Discovery Partnerships with Academia (DPAc) program. The other one has been concluded last December with the Fred Hutchinson Cancer Research Center. In the U.K. GSK currently has DPAc collaborations in place with Cambridge University and the University of Dundee.
Financial terms: Under the terms of the agreement, GSK will provide research support to Vanderbilt for three years, additional payments for meeting project milestones and a share of royalties. Cone’s lab will continue research on the receptor supported by NIH grant DK070332.
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