Descrizione del progetto
Esaminare la sclerosi laterale amiotrofica come un disturbo successivo alla nascita
La sclerosi laterale amiotrofica (SLA) è un disturbo neurodegenerativo fatale e incurabile con un’insorgenza in età matura. La debolezza muscolare si evolve rapidamente in una paralisi generalizzata e conduce alla morte nell’arco di 2-3 anni. Nonostante le conoscenze considerevoli disponibili sugli individui adulti, i successivi fallimenti clinici suggeriscono che gli attuali metodi di trattamento possono non essere pertinenti. Il progetto ADELE, finanziato dall’UE, intende dunque esplorare la SLA come una malattia dello sviluppo che si radica durante le fasi critiche dello sviluppo di una persona. A tal fine, esso indagherà le dinamiche della rete spaziotemporale in neonati murini con SLA e condurrà uno studio comportamentale sull’integrazione propriocettiva. Esso identificherà ulteriormente i farmaci che modulano l’attività per condizionare il corso della malattia. Il progetto fornirà informazioni preziose circa lo sviluppo e il trattamento della SLA.
Obiettivo
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disorder caused by the loss of motoneurons in the brain and spinal cord. Each year, ALS is responsible for three-five deaths per 100000 people. ALS initiates in mid-life by muscle weakness, evolving rapidly into a generalized paralysis that leads irrevocably to death within 2-3 years of clinical onset. Despite an exploding knowledge of pathological processes acquired in adult subjects, successive clinical failures suggest that our way to consider and treat the pathology may not be the most pertinent and effective. The idea that the pathology can originate during development has received very little attention, while in the post-natal period the fundamentals of the sensorimotor system are being laid, its completeness will be central for the rest of our days. ADELE project proposes to explore ALS as a developmental disease that take roots during critical developmental stages when the synchronized activity of sensorimotor circuits is established, and that subclinical threshold defects remains silent before reaching a clinical break point. This conceptual progress, with diagnostic and early therapeutic implications, can be made possible with the recent access to network activity of the spinal cord in rodent neonates. ADELE proposes to 1) investigate the spatiotemporal network dynamics in ALS mouse neonates by recording field activity using multi-electrode array along the spinal laminae, 2) to complete this approach by behavioral study of proprioceptive integration, which is detrimental for spinal circuitry function and 3) identify activity modulating drug to restore early spinal network dynamics and subsequently influence the course of the disease. Our multidisciplinary strategy will fill knowledge gaps with the goal to propose new therapeutic intervention and open up new horizons for the patients.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF-GF - Global FellowshipsCoordinatore
75654 Paris
Francia