Objective
Neuronal loss and malfunction underlie a wide variety of the neurological disorders that can afflict human populations. Conditions as diverse as Dementia, Parkinson's disease, Huntington's Chorea, Stroke and traumatic injury to the brain and spinal cord collectively have devastating effects on significant sections of the community. Much progress has been made in beginning to understand the mechanisms involved in the various pathological processes but their amelioration and cure remain targets for many neuroscientists. In addition to the many chemotherapeutic interventions that are presently being derived and tested, the ex vivo approach of implanting living cells to the brain for replacement of lost neurons or to promote functional recovery has had demonstrable effectiveness in both experimentally contrived neuronal deficits and, to a much more limited extent, in naturally arising human disorders. In this latter context human foetal cells have been successfully used as replacement therapy for Parkinson's disease patients but the logistic and ethical problems of finding sufficient numbers of the required cells for the large number of individuals that need treatment are insurmountable. In these circumstances the possibility of how, in tissue culture, to establish and expand the therapeutic cells needs exploration. The purpose of the present proposal is therefore to determine the in vivo efficacy of an ex vivo approach involving tissue cultured cells, genetically engineered to secure both their immortalisation and endowment with the capacity to liberate specific neurotrophic factors or neurotransmitters, which can be used for sustainable and safe remediation of neuronal deficits. The proposed project is a continuation and expansion of the preparatory award (proposal NLBT-ST-3046), which was awarded to two of the main contractors. Four main contractors, two SMEs and two academic groups and two associated contractors, one SME and one academic, from six European Community States constitute the proposing consortium. The two main academic groups are world leaders in their fields, cell therapy for neuronal disorders and viral vectors as instruments of gene therapy, and the main industrial collaborators are unique in Europe among BIOTECH companies in their specific interest in the Central Nervous System. The overall strategy will be to derive and use immortalised rat or human cell lines either alone or after genetic transduction with genes deemed to have beneficial products. These cells will be implanted with therapeutic and/or preventive intent into the brains of normal or immuno-suppressed rats that have defined neurological deficits. These abnormalities will be chosen to represent dementia, Parkinson's disease and Huntington's Chorea, though it should be emphasised that the principles involved could relate to other neuro-degenerative conditions. The models will be used mainly to demonstrate prevention of or recovery from disease as a consequence of secretion by the introduced cells of specifically engineered neurotrophic factors, particularly Nerve Growth Factor (NGF), Glial cell line Derived Neurotrophic Factor (GDNF), Neurturin (NTN) and Cilary Neurotrophic factor (CNTF).
The goal at the end of the project will be to have obtained and tested immortalised human cell lines which are candidates for large scale transplantation in human patients with a variety of neuronal disorders. This, the consortium believes, is innovative, feasible, safe and offers unique possibilities for the development of commercial opportunities for neural transplantation in Europe and globally.
Key words: Cell based gene therapy, neuro-degenerative diseases, neurotrophic factors, therapeutic cell lines.
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 dementia
- medical and health sciences basic medicine neurology parkinson
- medical and health sciences clinical medicine transplantation
- medical and health sciences medical biotechnology cells technologies
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Coordinator
223 62 Lund
Sweden
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