Descrizione del progetto
Sclerosi laterale amiotrofica: il ruolo dei motoneuroni superiori
La sclerosi laterale amiotrofica (SLA) è una malattia neurodegenerativa rara e incurabile che colpisce i motoneuroni che controllano i movimenti dei muscoli volontari. La SLA porta alla degenerazione dei motoneuroni superiori e inferiori, con prognosi grave e morte del paziente entro 2-5 anni dalla diagnosi. Il progetto CorticALS, finanziato dal Consiglio europeo della ricerca, intende studiare il ruolo dei motoneuroni superiori nella SLA. Esplorando la disfunzione e la perdita di questi neuroni, l’obiettivo è quello di svelare i meccanismi molecolari che possono essere presi di mira nel contesto di nuove strategie terapeutiche che proteggano o sostituiscano questo specifico tipo di neuroni. Questo approccio innovativo potrebbe fornire indicazioni preziose e far progredire i potenziali trattamenti per i pazienti affetti da SLA.
Obiettivo
Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset neurodegenerative disease of the motor system, with a prevalence of 2-3/100 000. In spite of intensive research efforts, ALS remains an incurable disease and presents with a very severe prognosis, leading to patient death within 2 to 5 years following diagnosis.
At the cellular level, ALS is characterized by the combined degeneration of both upper motor neurons (UMN, or corticospinal motor neurons) whose cell bodies are located in the cerebral cortex, and that extend axons to the medulla and spinal cord, and lower motor neurons (LMN, or spinal motor neurons) whose cell bodies are located in the medulla and spinal cord, and that connect to the skeletal muscles. This dual impairment allows to discriminate ALS from other, less severe diseases affecting either UMN or LMN. Despite this precise clinical description, it is striking to note that preclinical studies have so far mostly concentrated on LMN, leaving aside the role of UMN in ALS.
This project aims at shedding light on the contribution of the dysfunction and/or the loss of UMN in ALS, in order to design and test new therapeutic strategies based on the protection and/or the replacement of this exact neuronal type. This innovative question has never been directly asked so far. Our working hypothesis is that specific neurodegeneration of UMN, in the course of ALS, does not represent an isolated side effect, but rather actively contributes to the onset and progression of the disease. Based on the discovery of new molecular players, and the development of alternative therapies, this original thematic has the ambition to provide clinicians and patients with new answers and new therapeutic assets.
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
75654 Paris
Francia