Objective
Objectives:
The purpose of this proposal is to create an animal model in mice for TTR-associated amyloidosis leading to FAP with the long-term goal to generalise the model for other amyloid disease.
Brief description:
Amyloidoses are diseases of protein conformation. 16 amyloidogenic proteins are known of which the a-amyloid precursor peptide in Alzheimer's disease and the plasma protein transthyretin (TTR) in different forms of familial amyloidosis are best known. Both are associated with neurodegenerative lesions for which there is no cure. They both affect quality of life of individuals and causes large costs for the health care system.
TTR is associated with two types of amyloidosis occurring in different time periods of life. The senile form (Senile systemic amyloidosis, SSA) affects 25% of all individuals over the age of 80 years and has mainly manifestations in the heart. It is not a genetic disease, and it is thought that amyloid results from an inherent propensity of TTR to form amyloid with time. The genetic form is dominant autosomal and occurs earlier in life. More that 50 mutations of TTR are known and are associated with familial amyloidosis either with polyneuropathy (FAP) or cardiomyopathy (FZC), diseases with extracellular amyloid fibrils composed of TTR. The most frequent mutation is an exchange of valine for methionine in amino acid position 30 (TTR Met30). The specific objectives are:
1. study mechanisms for amyloid formation as result of point mutations of the TTR gene;
2. to study mechanisms for amyloid formation well as its consequences by developing a transgenic mouse model with overexpressed and mutated TTR genes and by studies of effects on cultured cells;
3. to develop diagnostic and therapeutical reagents.
The project involves creation of highly amyloidogenics mutants of TTR, studies of their structure, use of transgenic mice with amyloidogenic mutations, studies of pathophysiological consequences of amyloid deposits and the development of new therapeutic strategies based on the anthracycline derivative IDOX.
Keywords:
familial amyloidosis with polyneuropathy; cardiomyopathy; senile systemic amyloidodis; transthyretin; autosomal dominant; in vitro mutagenesis; transgenic mice; 3-dimensional structure; calorimetry; NMR; IDOX; anthreacyclin.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- natural sciences chemical sciences analytical chemistry calorimetry
- natural sciences chemical sciences organic chemistry amines
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Data not available
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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.
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.
Coordinator
901 87 UMEAA
Sweden
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.