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Chronic Inflammation and Fibrosis in EB Research Call

DEBRA International is now inviting expressions-of-interest for research into the processes of chronic inflammation and fibrosis (CIF) in epidermolysis bullosa (EB). Research into the role of these processes and aberrant wound healing in the initiation and spread of associated squamous cell carcinoma (SCC) in EB is also welcome.

Non-healing wounds leading to inflammation and fibrosis are interlinked consequences of EB, posing a major burden on patient quality of life, and in turn contributing to further complications including squamous cell carcinoma.

Greater understanding of the permissive environment of the altered extracellular matrix in EB coupled with modified interactions of proteins mutated in EB may provide novel targets for intervention to prevent, or slow, these processes. Through this call for research proposals, DEBRA wishes to support focused research to identify treatment targets, and to expedite development of effective preventative and therapeutic approaches.

The scope of eligible projects includes:

  • Research to develop a better understanding of the interplay of the processes of inflammation and fibrosis in chronic wounds specifically in EB, with the ultimate goal of treatments to prevent or slow these processes, and progression to SCC.
  • Clinical studies or clinical trials of therapies targeting chronic inflammation or fibrosis, or SCC initiation in any type of EB.

A recent priority-setting meeting identified detailed areas of research interest, including but not limited to:

  • Cellular and molecular players and events that drive CIF and SCC in EB:
    • Role of the major cell types and cell-signalling mechanisms involved
    • Role of destabilized basement membrane zone in regulating the composition of dermal matrix proteins
    • Role of the extracellular matrix composition, architecture and stiffness in creating a permissive environment for tumor development in EB
    • Cell plasticity – cellular markers to define temporal changes in cell identity and status/ function to identify targets for intervention.
    • Model systems to explore CIF and SCC specifically in EB.
  • Modified immune responses associated with CIF and carcinogenesis:
    • Role of the adaptive and innate immune system in non-healing EB wounds and carcinogenesis.
    • Identification of molecular targets involved in immunosuppression in EB
    • The role of collagen VII in communicating with immune and stromal cells to modulate immune response.
    • Drivers for carcinogenesis in EB, including the role of trauma and inflammation as triggers for SCC initiation
    • Targets for resolution of inflammation in clinically fragile patients
  • Fibrosis and tissue stiffness and contractures:
    • Inflammatory/ fibrotic mechanisms relevant to identification of novel interventional targets in EB.
    • Mucosal stiffness – identification of differing mechanisms or targets
    • Antifibrotic agents or cell-targeted therapy development
    • Biomarkers linked to variation in inflammatory / fibrotic response in wound healing: goals of identifying novel targets and/or stratifying patients for clinical trials.

The focus of the call is on chronic inflammation and fibrosis in EB, for the purpose of identifying possible targets for treatment or prevention, and preventing the initiation or spread of associated squamous cell carcinoma. Development of therapies that would address the underlying genetic defect, or established agents/methods that are used to treat squamous cell carcinoma fall outwith the scope of this call. Proposals in the latter categories may be submitted to the DEBRA International 'All-Priorities Spring 2019 Research Call'.

Key criteria:

  • Proposals must target chronic inflammation, fibrosis and SCC development in EB only.
  • Even if addressing fundamental biology, the proposal must demonstrate direct eventual relevance to the development of diagnostics or treatments to improve or limit inflammation and fibrosis in EB, or consequent initiation or spread of associated SCC.
  • The proposed project should be for a period of not less than 6 months, and not more than 3 years, with commensurate budgets.
  • Short-duration and longer-duration projects are equally welcome; projects should be resourced appropriately to address the issue under consideration.
  • Projects based on milestones/work packages that would allow part or staged funding will be considered positively.
  • Proposals should demonstrate the clinical and research expertise necessary for successful completion of the project; collaboration between research and clinical groups with complementary expertise is encouraged.
  • All proposals are subject to the same criteria of innovation, quality and feasibility of research, and ultimate patient benefit.

Key criteria for funding:

  • The application may be from a single research or clinical group, or a consortium; international collaboration is welcomed.
  • Consortia including collaboration with healthcare or biopharma industry are welcome.
    • the contribution of commercial partners must be clearly defined;
    • DEBRA cannot fund research that would be part of normal commercial R&D costs.
  • DEBRA does not normally fund capital costs.
  • Applications are welcome from all countries.
  • Lead applicants must be academic or clinical researchers employed in fully-salaried positions, for at least 12 months longer than the duration of the proposed project.
    • Principal investigators from collaborating research groups must be similarly employed.
  • While applications from co-applicants with equal status are welcome, the application must be submitted by a single lead applicant with whom DEBRA will correspond.
  • There is no upper limit to the proposed budget, but DEBRA will only provide a maximum of €250K to any one project. Proposals seeking larger-scale funding will be expected to source additional funding.
  • Any grant offer eventually made will be issued to a single institution, which is responsible for managing any subcontracting to collaborating institutions.

Co-funding

DEBRA funding (to a maximum of €250K) may be used to co-fund or match-fund grants from other funding bodies (e.g. from host institution, other charity or government bodies, or industry). The same criteria for deadlines, process of evaluation, award of funding, and progress reporting will apply in all cases. Any awards made by DEBRA will be in accordance with DEBRA Terms and Conditions. The amount of co-funding, terms and conditions of co-funding, and detail of what it will be used for, must be provided.

Application process:

There is a two-stage process of application:

  • Stage 1 Application period - Expression of Interest opens 30th July 2018.
  • The Stage 1 form to register an 'Expression of Interest' should be submitted via our online system by 17th September 2018 at 17:00 GMT.
  • If you are invited by DEBRA International to submit a Stage 2 'Full Application', further information will be sent to you. You will be informed (with feedback) if your Stage 1 application was unsuccessful.
  • The submission deadline for Stage 2 Full Applications is 17th December 2018.
  • It is anticipated that funding decisions will be made 15th April 2019.
  • All Stage 2 Full Applications will be subject to peer-review mediated by an Expert Panel convened for the purpose by DEBRA International: the final funding decision will be at the discretion of DEBRA International.