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Early defects in the dynamic of the spinal sensorimotor network: is ALS a post-natal neurodevelopmental disorder ?

Project description

Investigating amyotrophic lateral sclerosis as a post-natal disorder

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disorder with a midlife onset. Muscle weakness rapidly develops into a generalised paralysis and leads to death within 2–3 years. Despite the substantial knowledge available on adult subjects, successive clinical failures suggest that current treatment methods may not be pertinent. The EU-funded ADELE project therefore intends to explore ALS as a developmental disease that takes root during a person’s critical developmental stages. To this end, it will investigate the spatiotemporal network dynamics in ALS mouse neonates and conduct a behavioural study of proprioceptive integration. It will further identify activity-modulating drugs to influence the course of the disease. The project will provide valuable insight into the development and treatment of ALS.

Objective

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.

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 190 676,16
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 190 676,16

Partners (1)