Fractyl Health has created the Erase T2D task force, an academic-industry scientific partnership charged with advancing research on the role of the gut in metabolic disease to catalyse future discoveries that may inform how type 2 diabetes (T2DM) can be better understood and hopefully ‘erased.’ The Task Force built on decades of scientific investigation that has identified the critical role of the gut as a regulator of metabolic disease. The signalling mechanisms between the gut and the rest of the body are numerous and not yet fully delineated.
The first two research projects have now been initiated with Professor Alan Cherrington at Vanderbilt University and Professor Randy Seeley at University of Michigan. These two scientific research initiatives will establish a foundation of new evidence on nutrient sensing and signalling mechanisms in a segment of the intestine called the duodenum. The ambition is that this collaboration will lead to a deeper understanding of the possible causal relationship between a dysfunctional duodenum and the onset and progression of T2DM.
The first of these studies, led by Dr Alan Cherrington, Professor of Molecular Physiology & Biophysics, Professor of Medicine, and the Jacquelyn A Turner and Dr Dorothy J Turner Chair in Diabetes Research at Vanderbilt University School of Medicine, will focus on defining the gut-derived signalling pathways central to the development and progression of T2D.
“If the development of duodenal dysfunction as a consequence of high fat and sugar diets is an important event in the development of T2DM, we need to try to understand which duodenal changes could represent key causal steps in metabolic dysregulation and diabetes pathogenesis,” explained Cherrington.
The second study, led by Dr Randy Seeley, Professor of Surgery and Director of Michigan Nutrition Obesity Research Center at the Elisabeth Weiser Caswell Diabetes Institute in the University of Michigan Medical School, will focus on establishing a rodent model of duodenal mucosal disruption to help better define the mechanism of action of therapies targeting the duodenal mucosa.
“I am confident that we are taking the first steps in gaining a deeper understanding of the processes in the gut that lead to metabolic disease,” noted Seeley. “This will enable us to identify precursors and therefore ultimately build increasingly effective therapeutic approaches that could lead to a metabolic reset in patients with T2DM.”
These two studies will build upon a growing body of evidence by scientists around the world who have identified duodenal dysfunction as a potential root cause of metabolic disease (Aliluev et al; Duca et al). In spearheading this partnership, Fractyl Health is enthusiastic to begin this effort with academic partners who are icons in the field.
“Our ambition is to support the deep science that will lead to a greater understanding of the root causes of T2D. We know these studies are the beginning of a journey and will lead to findings – and more questions - we can use to define our next steps in the process of discovery,” added Dr Harith Rajagopalan, Co-Founder and CEO of Fractyl Health.
Fractyl Health’s lead product candidate, Revita, is based on the company’s insights surrounding the potential role of the gut in metabolic diseases. Revita is designed to remodel the duodenal lining via hydrothermal ablation (i.e., duodenal mucosal resurfacing) to edit abnormal intestinal nutrient sensing and signalling mechanisms that are a potential root cause of metabolic diseases.
In April 2016, Revita received a CE mark from the European Union. In the United States, Revita is for investigational use only and has received Breakthrough Device designation from the FDA to improve glycaemic control and eliminate insulin needs in T2D patients who are inadequately controlled on long-acting insulin.
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