H2020Индивидуална стипендия2018–2020

EpiPur · The ATP-P2X7R axis: a target for drug-refractory epilepsy

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

Период: 2018-01-01 → 2020-01-12
Финансиране от ЕС: 175 866 €
Участници: 1
Схема: MSCA-IF-EF-ST

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Накратко на български

Връзката между молекулата ATP и рецептора P2X7 се анализира чрез опити с мишки, за да се разбере как се развива епилепсията. Това е важно, защото помага да се обясни защо при някои пациенти стандартните лекарства не действат.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

The ATP-P2X7R axis: a target for drug-refractory epilepsy

"Epilepsy is a debilitating neurological disorder, with multiple causes. Currently, treatment for epilepsy includes only drugs which control seizures, rather than tackling the underlying causes. Further, approximately 30% of epilepsy patients are resistant to all available drugs. Epilepsy which develops following an acute insult to the brain, such as a seizure or head injury are particularly commonly associated with resistance to drugs. Understanding the processes which lead to the brain becoming chronically epileptic and the causes of drug resistance is important for developing solutions. When the brain is mechanically injured, deprived of oxygen, deprived of blood or hyperexcited, ATP, a molecule involved in providing energy to cells, is released into the extracellular space. Here, it acts as a trigger for inflammation which is important for limiting damage to local sites, killing pathogens, removing debris from damage, etc. Inflammation, however, when chronic, can contribute to pathology. It has previously been demonstrated that inflammation contributes to the development of epilepsy and is involved in resistance to antiepileptic treatments. The purpose of this project was to investigate the contribution of ATP to this process via the ATP receptor, P2X7, which has been widely reported as a ""gatekeeper"" of inflammation. This has involved characterizing ATP release in the brain during and following seizures and investigating the contribution of P2X7 to epilepsy and resistance to anti-convulsants, using an array of transgenic mice and P2X7-targeting drugs. The overall objective of the project was to characterise the role of the ATP-P2X7 axis in drug-resistance and development of epilepsy and test methods for potentially intervening."

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

Цел на проекта

Current epilepsy therapies, based on mediating excitation or inhibition have no impact on disease progression and are ineffective in over 30% of patients, demonstrating the urgent need for therapies with different mechanisms of action. An exciting concept is that increased hyperexcitability states and network changes are caused and maintained by a sustained glial activation.The ATP-gated P2X7 receptor (P2X7R), a gatekeeper of inflammation, has recently emerged as a promising target for epilepsy, showing anticonvulsant and disease-modifying properties in animal models. To bring P2X7R further towards a clinical application, however, important gaps in our understanding must be filled. Evidence for ATP release in the brain during seizures is currently lacking, the cell types involved in pathological P2X7R activation must be determined, and whether results from rodent models can be replicated in human tissue must be tested. Recent technical advances now bring the answers to these questions within reach. EpiPur brings together a team of experts in purinergic signalling, industrial partners specialised in the development of P2X7R antagonists and epilepsy clinicians. Biosensors will be used to record ATP in vivo with high sensitivity and temporal resolution; new transgenic mouse lines will be used to elucidate the subcellular expression and cell-specific disease contribution of P2X7R. Newly developed P2X7R antagonists will be tested in brain tissue resected from epilepsy patients. This highly interdisciplinary and intersectoral approach will add a significant contribution to the understanding of neuroinflammatory processes in disorders of the CNS. Further, the skills acquired during the research project, the excellent training record of the supervisor and host institution and the outstanding resources for learning and development available at RCSI will give me the tools necessary to achieve research independence.

Оригинален текст от CORDIS (на английски).

Участници

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