1- Scientific context and project objectives

The scientific context of the project is the development of diagnosis, research and therapeutic follow-up tools for a group of neurodegenerative diseases affecting the white matter of the central nervous system (CNS): leukodystrophies. This white matter is at the heart of the CNS communication network. Its malfunction is therefore what causes severe, sometimes fatal, disability, usually manifesting in children or young adults. They are associated with a high risk of intra-family recurrence due to their genetic origin. Concomitant progress made in the fields of brain imagery by nuclear magnetic resonance (IRM), human genetics and neurobiology prompted us ten years ago to develop research units (UMR 384 INSERM-UA) and management units (Clermont-Ferrand University Hospital) for these diseases. Clermont-Ferrand has taken the lead in this area by coordinating the research networks at national level (leukoFrance, National Hospital Programme of Clinical Research (PHRC) 2002, 2005), European level (European Network on Brain Dysmyelinating Disorders) and international level (PMD Task Force). Under the “rare diseases” plan, the French Health Ministry has officially labelled and equipped Clermont-Ferrand University Hospital as a national reference centre firstly for the molecular diagnosis of these diseases (Professor Isabelle Creveaux, Medical Biochemistry) and secondly for the assessment and treatment of patients (Professor Odile Boespflug-Tanguy, Medical Genetics). The purpose of the programme put forward is to create an information system with which the data generated by clinical approaches from imagery, molecular biology and biological resource banks can be interfaced. This will optimise the follow-up and treatment of patients and step up research on identifying the pathological processes involved and therapeutic strategies. This information tool must also create interfaces for inputting data from national and international partner sites of the Clermont-Ferrand site in order to strengthen its role as coordinator.

2- Project description

Due to this multidisciplinary approach, the data generated is highly disparate, requiring the creation of several interconnected databases enabling all types of retrieval by complex queries. Four interconnected systems will be developed within this programme: an image server with associated processing tools, a medical annotation platform, a biological database (biological/genome/transcriptome/proteome resources) with associated bioinformatics tools and a work session platform allowing all of the tools to be used jointly. Bioinformatics, image processing, signal processing techniques and statistical order analysis are required to get the whole system up and running effectively. All of the basic tools used exist and have been tested and validated. They are not therefore innovations as such. That said, using them together within a single information system is a new concept and stands clearly apart from existing tools that can only process one piece of information at a time and in a limited manner. This project will allow a large volume of data to be processed sequentially with high-level scientific processing tools.

3- Public or controlled use

The tool developed will be for public use, but the data generated and stored by this system will be accessible to accredited specialists only (doctors, researchers, technicians) in order to maintain the necessary confidentiality of medical data, even anonymised data. The original tools of this information system, developed on the model of leukodystrophy study, may nevertheless be duplicated freely.

4- Expected results

The main objective of the programme is to create the whole of the information system (tools and data) for studying leukodystrophies. This will enable the necessary tools for implementing the national PHRC obtained in 2005 to be set up in the short term. This work aims to determine the natural history and follow-up parameters of leukodystrophies associated with mutations of the PLP gene with a view to setting up therapeutic strategies at the INSERM-approved Clinical Investigation Centre (CIC). These strategies are currently being tested on animal models in close partnership with INRA-Theix’s “small animal” NMR platform in the Federative Research Institute Santé Auvergne and Neuronax company, which is researching a molecule discovered in the INSERM-UA mixed research unit 384, with neuroprotective and neuroreparative properties. This information system should also retain Clermont-Ferrand University Hospital’s status as a national reference centre by enabling epidemiological studies and cohort follow-up studies of these diseases to be carried out there and at its national and international partners via the Web interface. This original tool will therefore consolidate Clermont-Ferrand’s leading position and lead to a wide range of national (PHRC, National Research Agency - rare diseases plan) and European (FP7) research programmes being submitted. In addition to leukodystrophies, the information system produced may be applied to other diseases in partnership, on the national plan, with the rare diseases group of scientific interest and, on the Clermont site, with the CIC, the Clinical Pharmacology Centre (CPC), the Pain Treatment and Assessment Centre (CETD), the Cancéropole and the future Auvergnat Centre of Biological Resources (CRB). The purpose is to demonstrate the necessity and how feasible it is to standardise and professionalise data exchange between the various research bodies, whether they be public or private.

LifeGrid, the regional information system