Repurposing of antidiabetic agents and identification of disease biomarkers by lipidomics analysis in a novel zebrafish model of cln8.

The neuronal ceroid lipofuscinoses (NCLs) are orphan, rapidly fatal diseases in children and adults with few therapeutic options available. This proposal intends to raise hopes to investigate the repositioning of antidiabetics as valuable agents that may prevent or reduce the cognitive decline and neurodegeneration, in a novel zebrafish model of cln8, which will hopefully become a powerful tool to overcome the lack of the effective therapeutic approaches in CLN8 as in other NCLs. We will use zebrafish a simple cost-effective model, to assess the efficacy of already FDA/EMA- approved drugs for pediatric use, before scaling up to more expensive mammalian systems, and will offer the opportunity to accelerate drug discovery to halt or delay neurodegeneration. Moreover, we will define potential lipid biomarkers of disease through life span, but also the identification of new druggable targets involved in lipid metabolism, driving future drug development. The overall goal is to offer new therapeutic opportunities to promote better quality of life, in NCL patients.