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Senolytics repurposing in childhood refractory epilepsies

Project description

Repurposing anti-senescence medications for epilepsy

Focal cortical dysplasia (FCD) is a rare neurological disorder caused by abnormal brain development and is associated with structural malformations in the cerebral cortex. It is a major cause of drug-resistant epilepsy, particularly in children, resulting in recurrent seizures. Somatic mutations in the mTOR pathway are often encountered in brain cells of FCD patients, underscoring its potential role as a therapeutic target. The mTOR pathway is involved in cell survival and its activation may allow senescent cells to survive. The ERC-funded EpiSen project proposes repurposing senolytic drugs which selectively eliminate senescent cells with dysfunctional survival pathways. This strategy could revolutionise epilepsy treatment and improve patient life.

Objective

Epilepsy is a frequent neurological disorder characterized by recurrent seizures resulting from hyperexcitability and hypersynchrony of neuronal networks. Cortical malformations, including Focal Cortical Dysplasia (FCD), are rare sporadic diseases that cause early-life drug-resistant seizures for which surgery is the only therapeutic option to control seizures. Surgical inaccessibility and failures are significant clinical drawbacks. This emphasizes a critical and urgent need for new precision-based therapies for this debilitating childhood disorder.

In recent years, my team contributed to revealing that FCD are caused by brain somatic mutations in genes belonging to the mTOR pathway, a signaling cascade regulating key physiological cell functions such as growth, proliferation, and metabolism. During the course of my ERC-funded project, we discovered specific biomarkers in both human and mouse preclinical FCD brain tissues.

In EpiSen, we propose an innovative pharmacological strategy based on the selective elimination of mutated cells by repurposing available molecules, that are currently used in clinical trials in other diseases, for FCD-related epilepsy. We hypothesize that abnormal cells, once acutely cleared, will offer a prolonged benefit on seizures. Direct users include applied research groups, pharma companies, the medical community for clinical trials, and patient associations.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2022-POC2

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
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.

€ 150 000,00
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.

No data

Beneficiaries (1)

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