Descripción del proyecto
El papel de las motoneuronas superiores en la esclerosis lateral amiotrófica
La esclerosis lateral amiotrófica (ELA, o ALS por sus siglas en inglés) es una enfermedad neurodegenerativa rara e incurable que afecta a las motoneuronas que controlan los movimientos musculares voluntarios. La ELA provoca la degeneración de las neuronas motoras superiores e inferiores, lo que conlleva un pronóstico grave y la muerte del paciente al cabo de dos y cinco años tras el diagnóstico. El equipo del proyecto CorticALS, financiado por el Consejo Europeo de Investigación, pretende investigar el papel de las neuronas motoras superiores en la ELA. Al explorar la disfunción y la pérdida de estas neuronas, su objetivo es desentrañar mecanismos moleculares que puedan servir de diana en el contexto de nuevas estrategias terapéuticas que protejan o sustituyan este tipo neuronal específico. Este método innovador podría aportar información valiosa y hacer avanzar los posibles tratamientos para los pacientes con ELA.
Objetivo
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.
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
75654 Paris
Francia