Descripción del proyecto
Medicamentos sin interés comercial para enfermedades neurodegenerativas
Las paraplejias espásticas hereditarias (PEH, o HSP por sus siglas en inglés) son un grupo de trastornos hereditarios relacionados con la dificultad para caminar debido a la debilidad muscular y la espasticidad. Son causadas por la degeneración de las neuronas motoras y los tratamientos actuales no curan, sino que solo alivian sus síntomas. El proyecto Treat HSP, financiado con fondos europeos, tiene por objeto retrasar la evolución de la enfermedad mediante la prevención de la neurodegeneración. Sus investigadores probarán formas de disminuir la acumulación de lípidos en los lisosomas de las neuronas motoras en un modelo de ratón de la enfermedad. Los resultados abrirán nuevas posibilidades en el desarrollo de fármacos para mitigar las consecuencias debilitantes de las PEH.
Objetivo
Hereditary spastic paraplegias are a group of rare neurodegenerative diseases due to the degeneration of the long axons of cortical motor neurons. Some complex forms of the disease are also characterized by cognitive impairment. Currently, the only available treatments are symptomatic, act on the motor symptoms and do not prevent or delay the disease progression. There is therefore a strong demand of clinicians as well as of patients and their families for the development of any treatment that could delay the onset and/or the progression of the disease. We have developed a genetic mouse model of a complex form of hereditary spastic paraplegia, the SPG11 form that is extremely invalidating as the patients need to be taken in charge by families or specialized institutions. During the ERC Starting Grant program ER-HSP (GA – 311149), we have shown that this model presents both motor and cognitive impairments. We also identified accumulation of some lipid species in lysosomes as a putative therapeutic target to prevent neurodegeneration in this model. With the proof of concept grant, we plan to perform a preclinical trial to identify a possible treatment for this pathology. We have identified two different strategies to decrease the accumulation of lipids in neurons. In vitro assays have shown that both strategies can decrease accumulation of lipids in lysosomes. Importantly, both strategies can be translated into clinical trial in collaboration with industrial partners and represent potential new orphan drugs.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-POC - Proof of Concept GrantInstitución de acogida
75013 Paris
Francia