exploring the SYNErgistic effect of β-cell REGeneration and emerging IMmune intervention strategies to prevent and/or reverse type 1 diabetes

Project Details

Description

Preclinical type 1 diabetes (T1D) research has made important advances in recent years, but less progress has
been made in translating findings from in vitro and animal models into effective clinical interventions. INNODIA aims to achieve a
break-through in the way in which we study T1D to enable us to move closer towards prevention and cure of T1D. To this end,
INNODIA joins together the leading European experts from the fields of basic and clinical T1D research, four leading pharmaceutical
companies with strong expertise in the discovery and development of diabetes medicines and the two leading public organizations
involved in T1D research into one comprehensive collaborative consortium. The clinicians in INNODIA oversee T1D registries and
have access to large populations of children and adults with T1D and family members at increased risk of developing the disease.
The basic science researchers are experts in beta-cell pathophysiology, immunology, biomarker discovery, bioinformatics, systems
biology and clinical trial design. INNODIA will accelerate understanding of T1D through coordinated studies of unique clinical
samples and translation-oriented preclinical models. This should deliver novel biomarkers and interventions for testing in
appropriately designed trials, to be developed in active collaboration with regulators and patients. INNODIA provides access to
unique historical bio-repositories and will create the Clinical Sample Network, a clinical EU infrastructure to recruit T1D subjects at
diagnosis and at-risk relatives. These individuals will be deep-phenotyped and will provide bio-samples, allowing the establishment
of a ‘living biobank’ of subjects consented for recall. They will be characterized using standardized clinical, genetic and metabolic
phenotyping procedures, including prospective, longitudinal sample collection to facilitate novel biomarker discovery. Diverse
biological samples (blood, plasma, serum, urine, stools, etc.) will be collected at specific time points, following strict and
standardized operating procedures throughout the network. The large network of clinical partners in INNODIA has access to over
2,500 new onset T1D patients (children and adults) per year and the potential to recruit 1,500 and screen 5,000 high-risk subjects.
INNODIA will also create an EU-wide collection of pancreases and tissues from T1D and at-risk donors as well as T2D and
normoglycemic controls (EUnPOD). Strict standard operating procedures will be established for organ and tissue collection, in
collaboration with the US-based nPOD initiative. The samples collected from living donors and EUnPOD will be available for high
throughput screening discovery technologies in expert partner laboratories (academic and industry). Research in INNODIA will be
based on the following modules: 1. Beta-cell function (measuring/imaging functional beta-cell mass, early signs of beta-cell death);
2. Immunome to be performed in 3 Immune Hubs (flow cytometry, CyTOF, autoAbs, cyto- and chemokines, immune activation and
regulation); 3. Genome and transcriptome of beta- and immune cells (genotyping, epigenome, lncRNA, splice-variants, immune cell
subset and single cell analysis of TCR and transcriptome); 4. Proteome and peptidome (Immunome via MS (CyTOF), T-cell
phosphoproteome, beta-cell peptidome and proteome, serum proteome; 5. Metabolome-Lipidome (lipidomics and metabolomics).
Biobanks for samples available for later analysis (e.g. immune cells, stools for microbiome analysis) will be established. Novel in
vitro and in vivo models will be used, as well as a combination of existing techniques, made possible through the complementary
expertise of the basic research group. The focus will be on the exploration of novel biomarkers (recently discovered by INNODIA
partners) of beta-cell dysfunction or death, such as post-translationally modified proteins and alternatively spliced variants as well
as beta-cell specific miRNAs and metabolome signatures released in the surroundings when beta-cells are exposed to
inflammation. These novel biomarkers will be validated in human tissues (from the INNODIA Clinical Sample Network and EUnPOD),
human beta-cell lines, iPS-derived beta-cells as well as in humanized mouse models. Some of these novel biomarkers are ready for
immediate validation. Availability of humanized beta-cell lines and iPS-derived beta-cells with different genetic background and
humanized mouse models with different HLA profiles, will allow discovery and validation of novel biomarkers in different settings
and testing of novel intervention strategies arising from our previous research or as suggested by industrial partners of INNODIA
Short title or EU acronymSyneRegIm
AcronymAIIFUND98
StatusActive
Effective start/end date4/07/2231/08/24

Keywords

  • diabetes

Flemish discipline codes in use since 2023

  • Human and medical genetics not elsewhere classified
  • Other clinical sciences not elsewhere classified

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