University of Louvain discovers a protein capable of preventing diabetes and obesity
Patrice Cani, a WELBIO researcher at the Louvain Drug Research Institute of the University of Louvain (UCL, Belgium), and his team in cooperation with Willem de Vos, professor at the University of Wageningen (WU), have just made two major advances in the fight against obesity and type 2 diabetes. They have succeeded in halting the development of these two diseases in mice using two distinct treatments based on a bacterium called Akkermansia. If the tests prove to be positive among humans, these world-first discoveries will pave the way to the manufacture of a future drug that will make it possible to fight not just diabetes and obesity, but also cardio-vascular diseases and intestinal inflammation. This discovery has just been published in the prestigious scientific journal Nature Medicine.
Over the past 10 years, Patrice Cani, his team and Willem de Vos have been working on a bacterium called Akkermansia muciniphila, which, and the researchers at UCL were the first to demonstrate this, plays a key role in the battle against obesity and type 2 diabetes. This hypothesis made by the researchers at UCL in 2007 and proven in 2013, has been confirmed by other international researchers and is now an accepted fact. What did the team of Patrice Cani prove? That the use of live Akkermansia bacterium reduces the effects associated with obesity and diabetes in mice. The UCL researchers decided to produce Akkermansia in order to start tests on humans. The clinical investigation is carried out at the university clinics of Saint-Luc (UCL)1 since December 2015. The study is currently underway and they have just passed the first stage, namely proving that the use of the bacteria is safe and not dangerous for the human organism. Proof that the positive effects in mice also extend to humans still needs to be confirmed.
What is the innovative aspect of this research? Patrice Cani and his team, which includes Hubert Plovier (FNRS Research Fellow) have discovered that after pasteurisation (70°C), Akkermansia succeeds in halting the development of these two diseases in mice. Why pasteurising Akkermansia? The idea came from the researchers who were looking for a way of rendering the bacterium inactive without destroying it, so that it retained its properties while making the production thereof easier. The result came as a complete surprise to the researchers! Pasteurisation doubled the effectiveness of Akkermansia which eventually prevented the development of the diseases. Pasteurised Akkermansia was thus included in the clinical trial that is already underway and where it has also passed the safety stage.
The advantage of this discovery? Pasteurised Akkermansia is stable and is easier to administer to humans.
The researchers at UCL and Wageningen then wanted to understand why Akkermansia behaved differently when live and pasteurised. Which led them to their second major discovery: they isolated a protein present on the outer membrane of the bacterium. This protein also remains active (live) after being heated to 70°C. Pasteurisation therefore likely eliminates anything that is unnecessary in the Akkermansia bacterium and retains the protein, which probably explains its enhanced effectiveness. The researchers produced the protein (Amuc_1100*) by genetic engineering (procedure used in the manufacture of drugs) and then they tested it in mice. The results shows that it was as effective on diabetes and obesity as pasteurised Akkermansia. And there we have a second world first!
The discovery of this protein is also really promising as it also has a positive impact on our immune system: it blocks the passage of toxins into the blood, reinforces the immune defences of the intestine, and abolished the leaky gut syndrome for instance. Thus, the Amuc_1100* protein provides hope for the treatment of other diseases such as inflammation of the intestine that appears for instance in cases of stress, alcoholism, liver diseases and cancer.
Following these discoveries, the researchers at UCL and WU submitted several patent applications in order to protect them. A spin-off is underway to enable the large-scale production of both the Akkermansia bacterium as well as the protein with the aim of creating a drug capable of preventing diabetes and obesity in a first instance and then intestinal inflammation.
In order to complete this research, Patrice Cani benefited from financial support from several sources: the FNRS, the Baillet-Latour Prize, WELBIO and two European ERC grants (starting and proof of concept grants).
The project coordinators are looking for volunteers to take part in clinical trials. The participants must meet a number of very precise criteria however. The complete description of the profiles needed is available on the website created specially for the clinical research: www.microbes4u.be.
1 Prof. Jean-Paul Thissen, Prof. Michel Hermans, Prof. Dominique Maiter, Dr. Audrey Loumaye
A few statistics. In Belgium between 2001 and 2011, the number of people suffering from diabetes grew from 319,000 to 542,000, an increase of almost 70 % in 10 years. By the year 2025, 1 in 10 Belgians will be diabetic. More than 1 in 3, or more than 35 %, are overweight and 15 % obese (almost 1 in 5). In 2014, 1.9 billion of the world’s population were overweight, 600 million obese and 400 million diabetic.
Patrice Cani, Professor, UCL Louvain Drug Research Institute, mobile on request