Objective
Determine new possible functions of the neurotrophins, GDNF and Eph-ligands.
Examine whether these factors are able to prevent or compensate the degeneration of neurons in animal models of Parkinson' s or Huntington' s diseases.
Establish the basis for the development of a gene therapy approach for Parkinson' s and Huntington' s diseases, based on the grafting of neural progenitor cells expressing neurotrophic factors or on the direct administration of neurotrophic factors genes.
The present project covers the following topics:
Characterization of the role of the neurotrophins, GDNF and Eph-ligands on the survival and phenotype of embryonic neurons from the substantia nigra, locus coeruleus, raphe and striatum in culture.
Study of the role of the neurotrophins, GDNF and Eph-ligands in vivo, both during the postnatal development and in the adult. This will be done in three steps: a) Establishment of cell lines expressing high levels of Eph-ligands (NGF, BDNF, NT3, NT4/5 and GDNF cell lines are currently available). b) Characterization of the levels of expression of neurotrophic factors and their receptors in lesion models of Parkinson' s and Huntington' s diseases. c) Assessment of: the neurotrophic action of the cell lines in the intact brain, the protective effect of the factors on neurons in the lesion models, and the induction of compensatory responses in neurons after the lesion, including hypertrophy, sprouting or induction of specific enzymatic activities.
Investigate the function of these neurotrophic factors in mice with targeted deletions of the neurotrophin or trk genes. Possible alterations in the neurons of substantia nigra, locus coeruleus, raphe and striatum or in the innervation of their targets will be evaluated. Cell lines expressing neurotrophic factors will be used, when possible, to rescue the deficits induced by the neurotrophin knockouts.
Development of a strategy for the gene therapy of Parkinson' s and Huntington' s diseases. This includes two different approaches: a) The grafting of immortal neural progenitor cell lines engineered to express neurotrophic factors, which may integrate in the host brain and participate in the repair process. b) The immunoliposome-mediated transfection, that may allow high levels of direct transfer of neurotrophic factors genes to a defined population of cells in the host brain. In addition, the use of regulable promoters may enable to modify the levels of expression of the transgene in the brain with a pharmacological treatment to the animal.
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 parkinson
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
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Funding Scheme
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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
171 77 STOCKHOLM
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.