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Advancing knowledge to improve outcome in Paget’s disease of bone

Objective

Paget’s disease of bone (PDB) is a common skeletal disorder in people of European descent characterised by abnormal bone remodeling which disrupts normal bone structure causing pain, deformity, nerve compression syndromes and fractures.

The causes of PDB are incompletely understood. Genetic factors play a key role and some predisposing genes been identified but many remain to be discovered as do the mechanisms by which these genes influence bone cell function. Environmental factors also contribute but these are poorly defined, and it remains unclear how genes and environment interact to regulate susceptibility and severity. Further research is required to permit earlier diagnosis and to define the genetic and environmental factors that influence susceptibility to PDB so that new therapeutic strategies can be developed to improve outcome.

The Paget-Advance programme will progress beyond state-of-the-art by identifying new genetic variants that predispose to PDB by extended genome wide association studies and next generation sequencing of early onset familial cases where the causal genes are unknown. A genetic profiling test will be developed to facilitate early diagnosis and treatment. The functional mechanisms by which the variants affect bone cell function will be investigated using bioinformatics, cell culture studies and preclinical disease models. Potential environmental triggers will be explored focusing on the intestinal microbiome diet and biomechanical loading using preclinical disease models and prospective clinical studies.

The result will be to increase understanding of PDB and to facilitate earlier diagnosis and timely therapeutic intervention which will improve clinical outcome for patients and those at risk of the disease. The research will also have wider significance in advancing knowledge of the fundamental processes that regulate bone remodelling with potential spinoffs for other bone diseases.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2017-ADG

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Host institution

THE UNIVERSITY OF EDINBURGH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 422 623,00
Address
OLD COLLEGE, SOUTH BRIDGE
EH8 9YL Edinburgh
United Kingdom

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Region
Scotland Eastern Scotland Edinburgh
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 422 623,00

Beneficiaries (1)

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