Descrizione del progetto
Farmaci orfani per malattie neurodegenerative
Le paraplegie spastiche ereditarie sono un gruppo di disturbi ereditari associati a difficoltà nel camminare dovuta a debolezza muscolare e spasticità. Sono provocate dalla degenerazione dei motoneuroni e gli attuali trattamenti non forniscono cure ma alleviano solo i sintomi. L’obiettivo del progetto Treat HSP, finanziato dall’UE, è ritardare la progressione della malattia prevenendo la neurodegenerazione. I ricercatori testeranno modi per ridurre l’accumulo di lipidi nei lisosomi dei motoneuroni in un modello murino della malattia. I risultati apriranno nuove possibilità nello sviluppo di farmaci per mitigare le conseguenze debilitanti delle paraplegie spastiche ereditarie.
Obiettivo
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.
Campo scientifico
Programma(i)
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Meccanismo di finanziamento
ERC-POC - Proof of Concept GrantIstituzione ospitante
75013 Paris
Francia