AstraZeneca and the University of Pennsylvania join efforts to combat the global obesity and diabetes epidemics

Friday, 23 September 2011

AstraZeneca and the University of Pennsylvania, Institute for Diabetes, Obesity and Metabolism, have entered into a new collaborative research agreement to identify and develop small or large molecules that enhance differentiation of human adipose stem cells (hASCs) into cells with brown adipocyte properties that could potentially improve body weight control as well as help control glucose and lipid metabolism in type 2 diabetes patients.

The agreement allows the parties to work closely together in drug discovery and development granting AstraZeneca exclusive access to compound intellectual property and study data for any commercial purposes.

Type 2 diabetes and obesity are widely agreed to be the largest and most rapidly growing health problems in adults, amounting to a global epidemic. More than 1 billion adults and over 150 million children worldwide are overweight, of whom some 200–500 million are clinically obese1. Obesity is becoming increasingly recognised as the predominant risk factor for a range of diseases including: type 2 diabetes, cardiovascular disease, stroke and cancer. The latest estimates for diabetes indicate that there are almost 285 million diabetics worldwide, of whom more than 90% have type 2 diabetes. This figure is expected to rise to 439 million by 2030.

Finding compounds that can stimulate the development human adipose derived stem cells into brown adipose tissue could potentially provide novel approaches for managing obesity and its metabolic complications

Björn Wallmark, Head of CVGI iScience in AstraZeneca, Mölndal

Mammals have two main subtypes of fat cells, white and brown, known clinically as adipose tissue. White adipose tissue is specialised for energy storage, whereas brown adipose expends chemical energy in the form of heat. In rodents, brown fat can counteract obesity by safely burning off excess energy. Increased brown adipose function promotes a lean and healthy phenotype. Conversely, animals lacking brown adipose develop obesity and type 2 diabetes. Additionally white adipose tissue has stem cells for brown-like adipocytes which are interspersed within it and many druggable pathways can modulate adult stem cell differentiation. Recent PET-based imaging studies suggest that the amount of activated brown adipose in humans is inversely correlated with body mass index and age. These results suggest that brown adipose plays an important and unappreciated role in human energy balance.

The human adipose tissue-derived stem cells to support assay development and compound profiling within this collaboration will be provided by Indiana University.

The University of Pennsylvania, Institute for Diabetes, Obesity and Metabolism will provide access to their established platform/assay/technology for characterising phenotype of brown adipocytes for compound profiling during all phases of the project. They will also provide access to their skilled scientific group, led by Dr Patrick Seale, who has been exploring the pathways that control the development, differentiation and function of fat cells in normal development and in obesity. Dr. Patrick Seale is one of the two 2010 NIH New Innovator’s Award recipients of the university.

Michael J. Cleare, Associate Vice Provost for Research and Executive Director for the Center of Technology Transfer at the University of Pennsylvania. said “ the university is excited to be extending its important research partnership with AstraZeneca to include the field of obesity and Type 2 diabetes which are areas of much current concern".

It is anticipated that the combination of in depth knowledge in brown adipocytes biology with AstraZeneca’s drug discovery expertise will create possibilities of bringing new projects into the diabetes and obesity portfolio.

“Finding compounds that can stimulate the development human adipose derived stem cells into brown adipose tissue could potentially provide novel approaches for managing obesity and its metabolic complications”, added Björn Wallmark Head of CVGI iScience in AstraZeneca, Mölndal.

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