Objective
Recent evidence suggests that members of the VEGF family may be of therapeutic value for neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). Indeed, VEGF administration significantly improved the clinical outcome of animal models of A LS.
To further define the role of VEGF in motoneuron degeneration and in preparation of clinical trials, this project will investigate whether the expression of VEGF by the skeletal muscle might affect muscle atrophy and neuromuscular junction integrity in rodent models of ALS (SODG93A rats and mice).
This hypothesis will be investigated by inter-crossing SODG93A with transgenic mice over-expressing or lacking VEGF in the skeletal muscle. Alternatively, in vivo VEGF gene transfer to skeletal muscle fibers will be obtained by using vectors based on the Adeno-Associated Virus (AAV).
These models will represent a powerful tool to investigate whether muscle-derived VEGF can influence disease progression by maintaining muscle integrity or by inducing muscle regeneration and/or motor unit enlargement through axonal sprouting.
In addition, further work will be focused on the role of a novel VEGF homologue, VEGF-B, and its receptor Flt-1, in motoneuron degeneration, based on the observation that ALS mice lacking VEGF-B display an aggravated phenotype.
These mice will be therefore employed to determine whether VEGF-B exerts a neuroprotective support to motoneurons, atrophic effect on muscle fibers or a regulatory activity on glial cells.
Finally, a possible therapeutic role of VEGF-B in ALS will be explored, by either directly injecting the recombinant protein into the brain ventricles, or by intramuscular injection of AAV-VEGF-B vectors.
Collectively, these studies will generate insights with relevant implications to further optimize VEGF-based therapeutic strategies for ALS and other neurodegenerative disorders.
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 medical biotechnology genetic engineering gene therapy
- medical and health sciences basic medicine neurology amyotrophic lateral sclerosis
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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)
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.
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-5
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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
ZWIJNAARDE
Belgium
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.