A three-year research collaboration will see AstraZeneca and the French National Institute of Health and Medical Research (Inserm) investigate new therapeutic approaches to type 2 diabetes and chronic kidney disease (CKD).
The aim of the collaboration is to advance understanding of the biological mechanisms that underpin these conditions and develop new treatments based on this knowledge. Under the terms of the collaboration, each project will comprise a joint team of investigators that will work across Inserm sites in Toulouse and Paris, and AstraZeneca’s research hub in Mölndal, Sweden. The collaboration will focus on three areas:
Understanding mineralocorticoid receptor (MR) activity as a route to treating CKD
Excessive MR activation is an important mechanism in the development of CKD; however, this receptor also plays a crucial role in maintaining the body’s electrolyte balance. AstraZeneca, together with a team led by Professor Frederic Jaisser at the Cordeliers Research Centre (Inserm unit 1138) in Paris, will aim to better understand the complexities of MR activity as a potential treatment for CKD.
Enhancing tissue sensitivity to insulin
In healthy people, fat cells store lipids when the person is fed (state of energy excess) and release them in the fasting state. However, in obese and insulin-resistant patients, excess fat tissue leads to an uncontrolled release of lipids into the bloodstream. This leads to fat accumulation in tissues such as the liver and in muscle, triggering resistance to the action of insulin in those tissues and predisposing to type 2 diabetes. AstraZeneca together with a team led by Professor Dominique Langin at the Inserm/Paul Sabatier University Institute of Metabolic and Cardiovascular Disease (I2MC, Inserm unit 1048) in Toulouse will explore pharmacological ways to prevent the release of lipids into the circulation, normalise fat deposition and increase insulin sensitivity in peripheral tissues.
Exploring loss of insulin production
Beta cells are a type of cell found in the pancreas which produce and release insulin. In type 2 diabetes, both the quantity of beta cells and their ability to produce and secrete insulin are decreased. AstraZeneca together with a team led by Dr Raphaël Scharfmann at the Inserm/University Paris-Descartes unit 1016 "Cochin Institute" in Paris, will develop models of human beta cells which have lost their ability to produce and release insulin to better understand the biology of this effect and how it cn be corrected through treatment.
Marcus Schindler, Head of Cardiovascular and Metabolic Diseases Innovative Medicines unit, AstraZeneca said: “Over the last few years AstraZeneca has been focusing on pioneering research into cardiovascular and metabolic disease. By joining forces with Professors Langin, Jaisser and Scharfmann and their eminent research groups at Inserm, we strengthen further this ambition because their focus represents an ideal fit with our research strategy.”
Professor Christian Boitard, Director of the Inserm institute for Physiopathology, Metabolism and Nutrition, said: “This collaboration is focusing our efforts in beta cells, mineralocorticoid receptor and lipids handling by tissues. Combining the AstraZeneca and Inserm scientists, expertise and platforms represents a great opportunity for advancing research in these important fields, with the operational support of Inserm Transfert teams.”