Project description
Orphan drugs for neurodegenerative diseases
Hereditary spastic paraplegias (HSPs) are a group of hereditary disorders associated with difficulty in walking due to muscle weakness and spasticity. They are caused by degeneration of motor neurons, and current treatments do not provide cure but only alleviate symptoms. The scope of the EU-funded Treat HSP project is to delay the progression of the disease by preventing neurodegeneration. Researchers will test ways of decreasing the accumulation of lipids in lysosomes of motor neurons in a mouse model of the disease. Results will open new possibilities in drug development for mitigating the debilitating consequences of HSPs.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
75013 Paris
France