H2020Индивидуална стипендия2019–2021

EpimiRTherapy · Using human tissue to translate microRNA-based therapies for epilepsy

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-12-01 → 2021-11-30
Финансиране от ЕС: 184 591 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

МикроРНК молекулите в човешкия мозък се изследват чрез използването на специални антисенсови молекули (антагомири), за да се разбере как те влияят върху епилепсията. Това е важно, защото около 25% от пациентите не реагират на наличните лекарства срещу гърчове.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Using human tissue to translate microRNA-based therapies for epilepsy

Problem to be addressed: The overall research aim of EpimiRTherapy is to elucidate the mechanism of a novel disease-modifying therapy for epilepsy in the human brain. MicroRNAs are short non-coding RNAs which regulate protein levels in the brain. Certain microRNAs are strongly associated with epilepsy and their knockdown, using antisense molecules called ‘antagomirs’, has anti-seizure effects in rodents. However, antagomirs to treat neurological disease have never been tested in humans. EpimiRTherapy, for the first time, fills this gap: I will use state-of-the-art techniques to produce human brain slices from tissue surgically resected during temporal lobectomies for epilepsy. Why is it important for society: Epilepsy is a common neurological disorder which affects around 70 million people worldwide and manifests clinically as the susceptibility to recurrent spontaneous seizures. Roughly 25% of patients do not experience seizure freedom with available anti-epileptic drugs (AEDs). Additionally, adverse effects of AEDs are common due to their non-specific mechanisms of action, and no disease-modifying treatments are clinically available. Consequently, there is an urgent and unmet requirement for disease-modifying therapies in pharmaco-refractory epilepsy, to begin to alleviate the immense socio-economic burden caused by this disease. One of the most promising solutions is antisense knockdown of microRNAs (miRs). MiR levels are dysregulated in brain tissue from humans with epilepsy and in experimental rodent models, and correction of these alterations using antisense oligonucleotides (antagomirs) has disease-modifying anti-seizure effects in in vivo and in vitro (brain slice) models of the disease in rodents. The therapeutic effect of antagomirs has not been verified in human tissue and there remain several barriers to the translation of antagomir therapies for epilepsy to the clinic. Despite its immense promise, ant-134 is not currently being exploited or developed clinically, due to limited evidence of efficacy in humans. What are the objectives?: 1: Are antimirs taken up in human tissue? (Establish sufficient transfection efficiency). 2: Which human genes and pathways are targeted by miR-134? 3: What are the biophysical effects of miR-134 in human tissue?

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The overall research aim of EpimiRTherapy is to elucidate the mechanism of a novel disease-modifying therapy for epilepsy at single cell resolution in the human brain. MicroRNAs are short non-coding RNAs which regulate protein levels in the brain. Certain microRNAs are strongly associated with epilepsy and their knockdown, using antisense molecules called ‘antagomirs’, has anti-seizure effects in rodents. Antagomir targeting microRNA-134 (ant-134) is a particularly promising disease-modifying treatment for epilepsy, which could meet an urgent clinical need. However, antagomirs to treat neurological disease have never been tested in humans due to limited translational evidence. EpimiRTherapy, for the first time, fills this gap: I will use state-of-the-art techniques to produce human brain slices from tissue surgically resected during temporal lobectomies for epilepsy. I will use a combination of molecular techniques (acquired at the host lab in RCSI and through secondment to ICL) and electrophysiology, my core expertise, to determine the impact of ant-134 on the biophysical and transcriptional landscapes of human tissue and a network and single neuron level. This will be complemented with cutting edge systems modelling and imaging techniques acquired through collaborations. This fellowship, through advanced interdisciplinary and intersectoral training, will serve as a launchpad for reaching a position of professional independence and maturity, whilst at the same time facilitating a transfer of knowledge between myself, the host and the collaborators, by bringing cutting edge electrophysiology and human tissue processing techniques to RCSI and addressing an urgent and unmet clinical need for novel epilepsy treatments.

Оригинален текст от CORDIS (на английски).

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