Andalusia leads an international consortium to investigate cellular ageing as a key driver of type 1 diabetes
It will be carried out in collaboration with the Virgen Macarena University Hospital, the Seville Provincial Node of the SSPA Biobank; the Puerta de Hierro-Majadahonda Hospital in Madrid and the DiabetesCERO Foundation
The project, coordinated by Benoit Gauthier, researcher at the Fundación Progreso y Salud in Cabimer; and co-led by Enrique Samper, of the Spanish company Life Length SL, has a financing of more than 500,000 euros granted by Breakthrough T1D (formerly JDRF)
An international consortium led from Andalusia has launched a research project to determine if cell aging and cell death have a direct impact on the appearance and progression of type 1 diabetes, an autoimmune disease that destroys insulin-producing cells.
This study is carried out within the framework of a consortium that brings together public research institutions, hospitals, the company Life Length, and the DiabetesCERO Foundation in which patients are represented. This consortium is coordinated by Benoit Gauthier, principal investigator in Diabetes of the Progreso y Salud Foundation – entity under the Ministry of Health and Consumption.
Specifically, scientists will specifically study telomere shortening (a sign of cellular aging) as well as telomerase activity (an enzyme that adds DNA to telomeres to prevent them from shortening during division ) and senescence (death) of T cells (cells of the immune system) in the development of the disease. The aim is to identify biomarkers that can detect the disease at an early stage and explore new therapies capable of slowing its progression.
The project, called ‘Telomere Dynamics and Cellular Senescence in Type 1 Diabetes: Exploring Biomarkers and the Impact of LRH-1/NR5A2 Activation’, part of the hypothesis that premature shortening of telomeres - the structures that protect the ends of chromosomes - accelerates the aging of T cells, leading to inflammatory responses that could trigger the disease. “We know that telomeres are a marker of cellular aging and that immune cells from patients with type 1 diabetes show signs of early deterioration. We want to understand if this process starts before clinical symptoms appear and if we can reverse it, ”explains Gauthier.
Detect the disease in early stages
Within the framework of this study, in addition, a pilot project will be launched with a pioneering approach since it includes not only a systematic program of early detection of type 1 diabetes in presymptomatic phases in people at high risk (both first-degree relatives and those at high genetic risk) but also includes psycho-emotional evaluation and specific therapeutic education, thus being the only one of its characteristics in the national territory.
In this regard, scientists will analyze samples of blood from patients at different stages of the disease, including people at risk even without symptoms. The objective is precisely to determine whether telomeres and telomerase activity in T cells of T1D patients are affected and can serve as a diagnostic marker.
For this, they have the collaboration of María Asunción Martínez Brocca, head of the Endocrinology and Nutrition of the Virgen Macarena University Hospital and director of the Comprehensive Diabetes Plan of Andalusia; María Isabel García Sánchez, Technical Director and Coordination of the Node of the Virgen Macarena University Hospital of the Biobank of the Public Health System of Andalusia; María del Mar Romero Pérez, of the Pediatric Endocrinology Unit of the Hospital Virgen Macarena University; the DiabetesCERO Foundation; and also with Marta Marsal and Enrique Samper from the Madrid company Life Length, leader in telomere measurement thanks to its patented TAT® technology (Telomere Analysis Technology); and Macarena Alpañés, from the Endocrinology and Nutrition Unit of the Puerta de Hierro University Hospital in Madrid.
The project also study the behavior of a compound called BL001, discovered and patented by Gauthier's research group. It acts on a protein in the nucleus of cells (LRH-1/NR5A2) and, in animal studies that have already been carried out previously, has shown hopeful effects, since it has been observed that it helps reduce high blood sugar levels and favors a more balanced and less inflammatory immune response. The researchers now want to see if it can also protect the telomeres of T cells and slow their aging.
Type 1 diabetes is an autoimmune disease in which the body's own defenses destroy the beta cells of the pancreas, responsible for producing insulin. Although it is known that the system plays a central role in this process, the mechanisms that trigger the loss of immune tolerance are not entirely clear. Type 1 diabetes is one of the most common chronic diseases in childhood, with a high incidence in childhood and adolescence, although it can develop at any age.
This project, with an initial duration of two years, has been funded with more than 500,000 euros by the international association ‘Breakthrough T1D’, formerly known as JDRF. This is the fourth aid that this entity grants to Gauthier, which brings the accumulated support to about 2.5 million euros.
The initiative also has the support of the DiabetesCERO Foundation to connect patients with the project, thus consolidating a international and national alliance in type 1 diabetes research.
Source: Ministry of Health and Consumer Affairs