NOVATREAT project team develops a novel compound to reverse pre-diabetes

Part of the Microbiology of Human Health Laboratory (MICALIS – University Paris-Saclay, INRAE, AgroParisTech), the NOVATREAT project team is developing a novel compound to reverse pre-diabetes and plans to use this discovery to reduce the risk of pre-diabetes developing into type 2 diabetes.

Type 2 diabetes (T2DM) is a chronic disease, considered a global pandemic and a major public health problem. Accounting for 90% of cases of diabetes, it is due to a sustained excess of glucose concentration in the blood (hyperglycaemia). This is the result of a disturbance of the carbohydrate metabolism, linked in particular to an unbalanced diet rich in energy and to a significantly sedentary lifestyle. While it has a worrying rate of development in South America and Asia (China, Japan, etc.), T2DM is the subject of intense prevention campaigns in certain countries such as the United States. But “we do not yet have the same prevention culture in Europe on this subject, which should be brought to the forefront,” says Christine Delorme, a researcher in microbiology at the MICALIS unit and leader of the NOVATREAT project.

A decisive moment: the pre-diabetes phase

In 2021, an estimated 537 million people worldwide had diabetes. The diagnosis of the disease often comes late, especially because T2DM does not cause any painful manifestations. However, it is very difficult to achieve remission of T2DM. If it is identified at an early stage – in the pre-diabetes phase – when it is not yet a disease but just a risk factor, it is possible to stop it from progressing any further.

But the pre-diabetes phase is not very well known either. Every year, 5-10% of the pre-diabetic population develops T2DM, with a sharp increase in cases diagnosed in people under the age of 50. And only 5 to 10% per year manage to “revert”, i.e. to return to a normal glycaemic state, thanks to the adoption of a good dietary hygiene and regular physical activity. “But this discipline has to be applied over the long term and we have observed that it is often difficult to maintain,” comments Christine Delorme.

A chance discovery

To remedy this difficulty, Christine Delorme and her colleague Véronique Douard, a researcher in intestinal physiology at the MICALIS Institute, are working on the NOVATREAT project. Originally, in 2017, they collaborated on a project to study the anti-inflammatory properties of commensal bacteria in the gut. In addition to inflammatory bowel disease, obesity and metabolic diseases such as T2DM are also associated with tissue inflammation. To test the anti-inflammatory effect of these bacteria in such a context, the two researchers used an experimental model of diet-induced obesity and pre-diabetes in rodents. “This experiment led to the chance identification of a bacterial metabolite capable of reducing diet-induced hyperglycaemia.” It is an amino acid derivative.

Prematuration and a patent

Following this discovery, in 2018, the two researchers launched the TreatDiab therapeutic innovation project thanks to Université Paris-Saclay’s IdEx (Initiatives of Excellence) prematuration programme. This led them to file a patent in 2019 to use the bacterial metabolite in the prevention and treatment of glucose intolerance, also known as pre-diabetes. The project was also an opportunity to complete the first results and to start studying the mode of action of the metabolite. Preliminary results confirm that the metabolite helps regulate blood glucose in pre-diabetes animal models.

The launch of NOVATREAT

Christine Delorme and Véronique Douard are continuing their research and have designed technology integrating the bacterial metabolite with anti-hyperglycaemic action to reduce the risk of developing T2DM in pre-diabetic individuals. Since pre-diabetes is not a disease, this solution cannot be developed as medicine. The researchers are therefore focusing on a food supplement with a powerful preventive benefit, i.e. an established level of scientific proof. “Too many dietary supplements do not provide precise information on their modes of action, and we want to avoid this pitfall,” warns Christine Delorme.

In September 2020, they submitted a prematurity project to the Université Paris Saclay Poc In Labs call for projects and SATT Paris-Saclay POC’UP, which took them directly on to a maturation project. “Our initial results were sufficiently advanced and promising to enable us to move directly on to this stage of support,” notes Christine Delorme. For four months, with Vincent Juillard, a microbiologist at the MICALIS Institute, they co-constructed the NOVATREAT project as part of the Tech Transfer Programme. A team of about ten people was trained to support them. It includes INRAE/AgroParisTech researchers, legal experts, patent and marketing engineers from SATT Paris-Saclay and INRAE Transfert, and experts in regulation and product development. The project, validated by the investment committee, started in October 2021 and will continue until the end of September 2023. “This support was decisive in developing NOVATREAT, and also in carrying out a market study and dealing with the regulatory aspects related to the development of an active principle.”

Scientific validation of the anti-hyperglycaemic effect

In 2022, the team’s work confirmed the effectiveness of the metabolite on blood sugar regulation. It is effective on animals on a high-fat diet, as quickly as fifteen minutes after oral intake. “After absorption of the metabolite during an oral glucose tolerance test, the two-hour blood glucose level of the group that were given the metabolite was 14% lower than the group that did not have it,” enthuses Christine Delorme. Since the metabolite was found in the plasma of the animals, this also shows that it passes the intestinal barrier and spreads to peripheral tissues via the bloodstream. Using multiple approaches, the team also identified the mechanism of action of the metabolite.

Next step: regulatory compliance and industry partnerships

Building on this success, the team is now focusing on a regulatory approach. This is because the route for food supplements is different depending on the origin of the product and its consumption (age and quantity). “Our new compound is synthesised naturally by bacteria and plants, but not by humans. It is nevertheless found in human plasma via production by the intestinal microbiota, and via food. We are currently investigating this point by tracing a history of human consumption based on the presence of the metabolite in common foodstuffs,” says Christine Delorme. The regulatory file is expected to be completed by the end of 2023.

At the same time, in order to develop the marketing of the food supplement and to pursue the project until a health claim is made, the patent will be licensed either within the framework of the creation of a start-up, or to an industrialist already in place in the field. Action is underway.

Paris-Saclay University (French: Université Paris-Saclay) is a public research university based in Paris, France. It is one of the 13 prestigious universities that emerged from the division of the University of Paris, also known as the Sorbonne.

It is part of the Paris-Saclay project, which is a research-intensive academic campus, and is the main center for training and research within the technology cluster of Paris-Saclay. The University integrates several leading grandes écoles, faculties, colleges and research centers that are part of the world’s top research organizations in various fields.

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