ADELE · Early defects in the dynamic of the spinal sensorimotor network: is ALS a post-natal neurodevelopmental disorder ?
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2020-04-01 → 2022-03-31
- Финансиране от ЕС
- 190 676 €
- Участници
- 2
- Схема
- MSCA-IF-GF
Линиите свързват координатора с партньорите.
Накратко на български
Амиотрофичната странична склероза (ALS) се изследва чрез модели с мишки, за да се установи дали дефектите в гръбначния мозък възникват още в ранното развитие. Разбирането на този ранен произход може да разкрие причините за заболяването и да предложи нови терапевтични подходи.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Early defects in the dynamic of the spinal sensorimotor network: is ALS a post-natal neurodevelopmental disorder ?
Amyotrophic lateral sclerosis (ALS) is a progressively paralyzing neurodegenerative disorder usually fatal within 3 years of diagnosis. ALS affects motoneurons located in the motor cortex, brainstem and spinal cord. The incidence of ALS ranges between 2-3 per 100 000 person-years, with a median age of age comprised between 50 and 70 years. The majority of cases being diagnosed are considered sporadic, while approximately 10% of patients have a familial history of the disease. ALS causing mutations in Cu-Zn superoxide dismutase (SOD1) were the first to be identified and are among the most frequently found in familial cases. Transgenic mice that express ALS-causing mutations in SOD1 recapitulate the main traits of the human disease and represent therefore a reliable and informative model to comprehend pathogenic mechanisms. The vast majority of ALS research has legitimately approached this disorder as an adult condition. The concept that this disease can take root very early in the life of patients has received little consideration, while structural and fundamental sensorimotor functions are established during specific developmental window. Indeed, this critical period of spinal network organization being detrimental throughout the lifespan. Surprisingly, apprehending ALS as a developmental disease of sensorimotor network connectivity is a major conceptual step, both at the level of our vision to understand pathogenic mechanisms and especially at the therapeutic scale. Considering an early, infantile origin, sub-lethal aberrant network connectivity, escaping the vigilance of parents and clinicians, will provide new insight into ALS aetiology and open innovative therapeutic perspective. This MSCA aims to identify alterations in early spontaneous sensory-evoked electrical activities in the spinal cord and motor reflexes of neonatal ALS animals to propose innovative therapeutic intervention. A strong collaboration and a successful transfer of knowledge and know-how enable to explore physiological and behavioral aspects related to the hypothesis of a developmental origin of ALS. The objectives remain competitive and original, the ADELE consortium offers the possibility to explore these new perspectives to better understand and potentially propose new therapies for this devastating pathology.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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.
Оригинален текст от CORDIS (на английски).
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Данни: CORDIS, © Европейски съюз