281234 DEM-Child (A

The research in the DEM-CHILD project focuses on a group of the most common neurodegenerative diseases in childhood, the neuronal ceroid lipofuscinoses (NCLs). The NCLs are an etiologically and clinically heterogeneous group of autosomal recessive progressive paediatric encephalopathies, with a global incidence of 7-8 per 100,000 live births. These inherited diseases are characterised by dementia, epilepsy, and progressive physical decline, by profound neurodegeneration in the central nervous system and an early death of the patients. The NCLs are the main cause for childhood dementia in Europe, and since no cure is currently available, these disorders represent a serious social, medical, and economic challenge.

To date, the genes for fourteen forms of NCL have been characterised and novel gene functions revealed. Several lines of evidence suggest further gene loci remain to be identified, and that NCLs are under-diagnosed in many countries around the world. Due to their low prevalence, there is an overall lack of information, research, early diagnosis, treatment, and expert availability. Furthermore, due to broad genetic heterogeneity it is usually difficult to collect large numbers of clinically and genetically similar patients. As such, the potential to initiate the large therapeutic studies required for advances in treatment is rather limited.

The proposed project will therefore implement a novel network including the most prominent NCL researchers, both basic scientists and clinicians, in Europe, collaborating with Indian experts, to collect the world largest, clinically and genetically best characterised set of NCL patients. Furthermore, we shall build upon the information generated by the consortium researchers during the last ten years, to identify and characterise novel biomarkers and modifiers, and to develop novel therapies for NCL. The NCLs are defined as lysosomal storage diseases. Amongst all paediatric neurodegenerative disorders, they are especially suitable for development and monitoring of therapies. Excellent cell and animal models exist for this group of diseases, enabling the characterisation of pathological events, screening of disease modifiers and biomarkers required for the development of treatment strategies and monitoring their effects.