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.
Field of science
- /engineering and technology/other engineering and technologies/microtechnology/organ on a chip
- /natural sciences/biological sciences/genetics and heredity/rna
- /natural sciences/computer and information sciences/artificial intelligence
- /medical and health sciences/basic medicine/neurology/epilepsy
Programme(s)
Call for proposal
H2020-FETOPEN-2018-2019-2020-01
See other projects for this call
Funding Scheme
RIA - Research and Innovation actionCoordinator
X91 Waterford
Ireland
Participants (6)
8000 Aarhus C
8200 Aarhus N
2 Dublin
44121 Ferrara
1096 Lefkosia
33100 Tampere
