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Targeting common mechanisms of pathogenesis in diseases of sterol homeostasis associated with lysosome dysfunction; development of novel and rapidly translatable clinical therapies


"We have recently discovered a link at the cellular level between two rare pediatric diseases, Niemann-Pick C (NPC) and Smith-Lemli-Opitz Syndrome (SLOS). NPC is a disease where cholesterol and other lipids accumulate within the lysosome. SLOS is a multimalformation disease attributed to an inborn error of cholesterol synthesis, characterised by severe birth defects and neurological decline. Our data suggests that accumulation of a sterol precursor in patient-derived SLOS cells functionally inhibits the NPC1 protein, leading to an NPC disease-like phenotype that negates the therapeutic effect of elevated dietary cholesterol in SLOS. This discovery has important implications both conceptually and clinically. Based on these exciting observations, the fellow aims to:
1. Comprehensively characterise the similarities between NPC and SLOS at the cellular and whole organism level.
2. Determine the mechanism by which sterol accumulation inhibits NPC1 function and elucidate their role in regulating NPC1 activity.
3. Develop rapidly translatable therapies for SLOS based on currently available NPC therapies.
4. Discover clinical markers for SLOS for an upcoming clinical trial of miglustat.
A multidisciplinary and cross-collaborative research approach will be employed to investigate this unexplored link. The host laboratory is a world-leader in rare disease research, within a high-level research institute. Utilising her adaptability and expertise, combined with that of the host and their collaborators (academic and industrial), the fellow would make a substantial impact in this area of unmet clinical need. Collectively, rare diseases affect ~26 million people in the EU. This project meets an important and current FP7 Health thematic priority namely “Translating research for human health”. This fellowship will represent a significant landmark for the fellow’s transition from basic to translational research and her establishment as an independent scientist in an emerging field."

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Newport Road 30-36
CF24 ODE Cardiff
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 200 371,80
Administrative Contact
Eevi Laukkanen (Ms.)