Objective
The goal of this project is to enhance the technology used to detect and measure non-coding RNAs (ncRNAs) in blood, which will help us to find new biomarkers for Type 1 Diabetes (T1D). By analyzing blood samples from individuals involved in the INNODIA consortium project, we hope to discover novel biomarkers that can predict, monitor, and tailor treatments specifically for T1D. Ultimately, we also aim to trace these ncRNAs back to their originating cells. This could greatly improve our understanding and management of the disease.
Background Rationale
Type 1 Diabetes (T1D) is a serious autoimmune disease where the immune system mistakenly attacks and destroys the insulin-producing cells in the pancreas. This attack results in high blood sugar levels, requiring lifelong insulin therapy to manage. Although various treatments have been developed to target the immune system and the pancreatic cells, their effectiveness has been limited. However, recent strategies that address both aspects simultaneously show promise, though responses to these treatments can vary greatly among individuals. Understanding why some people respond well to certain therapies while others don't is key to developing personalized treatments.
A crucial part of managing T1D and personalizing therapy is identifying reliable biomarkers—molecules that signal the presence of the disease, track its progression, or measure the response to treatment. RNA, which plays critical roles in cellular processes and is similar to DNA, includes types known as non-coding RNAs (ncRNAs). These ncRNAs regulate many cellular functions and can be found in various biological fluids, such as blood. Recent findings suggest that ncRNAs can act like hormones, targeting cells far from their point of origin, which makes them ideal disease biomarkers. For example, ncRNAs from immune cells that attack the pancreas can contribute to the dysfunction and death of insulin-producing cells. Conversely, ncRNAs from insulin-producing cells can affect immune cells and other tissues, showcasing the complex interactions that might drive different aspects of T1D.
Despite these advancements, the role of circulating ncRNAs in the progression of T1D and their specific origins are still not fully understood or carefully studied. The challenge now is to identify these circulating biomarkers through a liquid biopsy approach, which would greatly aid in the stratification and treatment of T1D patients. However, this effort is complicated by technical challenges, the variability of RNA expression among individuals, and the complex nature of the ncRNA network in blood. Current technologies do not yet allow a comprehensive view of this landscape, and factors like how blood is collected and processed can further skew the levels of ncRNAs detected.
To overcome these hurdles, stringent and consistent procedures for collecting and processing blood samples have been implemented by the INNODIA consortium, which was established in 2015 specifically for small RNA research. This standardization helps reduce biases in sample collection. By combining these high-quality resources with advanced analytical methods, we aim to enhance our ability to discover and validate additional biomarkers for T1D.
Ultimately, this project seeks to refine the technology for detecting circulating ncRNAs and use these improvements to study blood plasma samples from individuals newly diagnosed with T1D, those at high risk, and those undergoing specific immunotherapies. By gaining a better understanding of T1D's complex nature at both the onset and earlier stages, and by identifying biomarkers that predict treatment responses, we hope to make T1D more predictable, preventable, and effectively treatable.
Description of Project
The main challenges in Type 1 Diabetes (T1D) are:
(1) It is hard to predict exactly when the disease will start (prediction of the symptomatic onset );
(2) People with T1D can show a wide variety of symptoms when the disease first appears, with different progression over time (heterogeneity of symptoms and disease managing);
(3) there is a need for personalized treatments that better match each person's unique response to the disease (precision medicine and therapy).
To tackle these challenges we need to identify biomarkers—measurable and accessible molecules in human blood —which can give us information on T1D individuals health status.
Non-coding RNAs, a type of molecule similar to DNA but mainly involved in regulating cellular functions, are particularly promising. These molecules are released from cells and can be found in all bodily fluids, such as blood plasma. This feature allows us to use them as biomarkers; thus, changes in non-coding RNA levels in certain cells can be detected through a simple blood test, a concept known as a “liquid biopsy”.
Non-coding RNAs in blood are part of a complex network and pinpointing their exact origin is challenging due to current technological limits and the intricate nature of blood components. Despite these challenges, we aim to get a clearer picture of these blood biomarkers to improve our understanding of T1D.
In our project, we will improve advanced methods to detect and measure the levels of these RNAs in blood samples from individuals newly diagnosed with T1D, those at high risk, and those treated with specific immunotherapies within the European INNODIA network. By analyzing blood from individuals at different stages of T1D development and treatment, we will identify novel groups of biomarkers that could help us monitor and potentially predict the disease’s progression from an early stage. We will also explore how these biomarkers change in response to treatments and over time by studying samples from T1D patients over a two-year period.
Additionally, by studying in-vitro the RNA released from various human cells under different conditions, we aim to trace the origins of these non-coding RNAs, enhancing our ability to detect and also understand their biological roles in T1D.
Overall, by improving our detection methods and understanding of these novel biomarkers through the INNODIA project, we aim to make T1D more predictable, preventable, and treatable.
Anticipated Outcome
We expect that this project will lead to significant breakthroughs in understanding T1D. Specifically:
(1) We expect to discover a set of new circulating ncRNA molecules that can be detected and measured through a simple blood test. These biomarkers could help predict the onset of T1D in high-risk individuals who test positive for one or more autoantibodies.
(2) We expect to discover a set of molecules to track how the disease progresses after its clinical onset, and aid in creating personalized treatments tailored to individual needs.
Relevance to T1D
This research is crucial for T1D as it tackles major challenges in managing the disease. By discovering new biomarkers, we aim to enhance our ability to predict when T1D will begin, monitor its progression after symptomatic onset, and customize future immunotherapy treatments for each patient. This could make managing T1D easier and potentially preventable, significantly improving the quality of life for those affected by the disease.