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A Personalised Living Cell Synthetic Computing Circuit for Sensing and Treating Neurodegenerative Disorders

Project description

Innovative diagnostic-therapeutic treatment for neurological diseases

Epilepsy is a severe and chronic brain disease characterised by intermittent seizures. Closed-loop implanted devices have the potential to reduce seizures in drug-resistant patients. However, their efficacy is limited and requires constructing devices from non-organic materials implanted in the brain. The EU-funded PRIME project aims to build 'living brain implants' that can detect transfer RNA (tRNA) fragment molecules in patients before a seizure occurs, and compute them to perform actuation. The actuation is in the form of seizure-suppressing treatment relying on engineering human cells to detect the tRNA fragment and trigger pre-emptive release of therapeutic molecules. The transformational diagnostic-therapeutic solution from PRIME can also be used for other neurological diseases.

Objective

There remain urgent and unmet needs for the treatment of neurological diseases. Epilepsy is a serious, chronic brain disease characterized by recurrent seizures. Closed-loop, implanted devices offer ways to reduce seizures in drug-resistant patients but their efficacy is poor and they interrupt seizures only after they begin. PRIME capitalizes on a breakthrough discovery that transfer RNA (tRNA) fragments, a novel class of noncoding RNA, increase in patients in advance of when a seizure occurs. We propose to engineer human cells to respond to tRNA fragment elevations as the trigger for pre-emptive release of glial-derived neurotrophic factor (GDNF), a seizure-suppressing and disease-modifying treatment. Artificial Intelligence (AI) algorithms will be used to integrate OR or AND logic gate functions in the switching process, depending on the quantity and type of tRNA fragments and timing of their release in a given epileptic network and a second, fail-safe calcium-dependent pathway will allow GDNF release in the event of a breakthrough seizure. This enables a precise level of personalization in the design of the bio-computing cells, which will be encapsulated into a membrane device within the microenvironment scaffold, enabling the engineered cells to co-exist with natural brain tissue. Validation of the bio-computing cells will be tested in both in vitro microfluidic organ-on-a-chip as well as in vivo tests for effects on spontaneous seizures in rodents with epilepsy. PRIME’s results will provide a transformational diagnostic-therapeutic treatment for epilepsy and other neurological diseases that feature disrupted neuronal network function.

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RIA - Research and Innovation action

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Call for proposal

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(opens in new window) H2020-FETOPEN-2018-2020

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Coordinator

SOUTH EAST TECHNOLOGICAL UNIVERSITY
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.

€ 706 875,00
Address
CORK ROAD CAMPUS WATERFORD
X91 K0EK WATERFORD
Ireland

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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.

€ 706 875,00

Participants (6)

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