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An induced pluripotent stem cell-based neuronal model of Spinocerebellar ataxia

Objective

The spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders defined by a loss of motor coordination. No effective treatments exist, and there is thus a pressing need for suitable models in which to study disease progression and to screen potential therapies. Induced pluripotent stem cells (iPSCs), which are capable of differentiation into any cell type of the body, offer the opportunity to study neurodegeneration in vitro. The proposed study aims to be the first in Europe to establish an iPSC-derived model of cerebellar disease, focusing on two genetic subtypes of SCA - SCA14 and 41. Increasing evidence points towards common pathological pathways shared across multiple SCA subtypes, which could provide novel therapeutic targets. There is also evidence to suggest that abnormalities in Purkinje cell development may contribute to the pathogenesis of the SCAs. This model will thus be used to elucidate the molecular mechanisms underlying common SCA-causing disease pathways, and to unravel the neurodevelopmental aspects of these diseases, in order to develop early-intervention therapies. Preliminary results indicate successful differentiation of iPSCs into cerebellar progenitor cells, using a protocol I have optimised. Following terminal differentiation, these cells will be investigated for common disease phenotypes and developmental defects, using a combination of transcriptomic, biochemical, and electrophysiological methods. Results will be validated by comparison with post-mortem brain samples and ataxic mouse models. By adapting this differentiation strategy to a format amenable to high-throughput screening, a pipeline will be established for the identification of novel therapeutic compounds. This groundbreaking study will enable the investigation of mechanisms which render the cells of the cerebellum particularly sensitive to degeneration, as well as providing a platform for pre-clinical screening of therapeutics for neurodegenerative conditions.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

MSCA-IF-EF-ST - Standard EF

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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) H2020-MSCA-IF-2015

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
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.

€ 195 454,80
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
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.

€ 195 454,80
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