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. PRIMEs results will provide a transformational diagnostic-therapeutic treatment for epilepsy and other neurological diseases that feature disrupted neuronal network function.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicineneurologyepilepsy
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesmathematicspure mathematicsarithmeticsprime numbers
- engineering and technologyother engineering and technologiesmicrotechnologyorgan on a chip
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Funding Scheme
RIA - Research and Innovation actionCoordinator
X91 K0EK Waterford
Ireland