Description du projet
Médicaments orphelins pour les maladies neurodégénératives
Les paraplégies spastiques héréditaires (PSH) sont un groupe de maladies héréditaires associées à une difficulté de locomotion due à une faiblesse musculaire et à une spasticité. Elles sont causées par la dégénérescence des neurones moteurs et les traitements actuels n’apportent pas de remède mais permettent seulement de soulager les symptômes. Le projet Treat HSP, financé par l’UE, vise à retarder la progression de la maladie en prévenant la neurodégénérescence. Les chercheurs testeront des moyens de réduire l’accumulation de lipides dans les lysosomes des neurones moteurs dans un modèle murin de la maladie. Les résultats ouvriront de nouvelles possibilités de développement de médicaments visant à atténuer les conséquences invalidantes des PSH.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
ERC-POC - Proof of Concept GrantInstitution d’accueil
75013 Paris
France