The importance of a clinical database and a biobank for leukodystrophies: an interview with Professor Odile Boespflug-Tanguy

Written on Wednesday 3 April 2013

When did you start to gather clinical data and biological samples for leukodystrophy patients?

We began collecting biological samples in parallel to clinical data as of 1992 thanks to an Inserm clinical research network and then thanks to the support of the ELA association, the European ENBDD project, the research foundation and the Clermont Ferrand University Hospital Centre (FEDER project).

What were the major development stages for these tools?

The first 10 years were devoted to setting up national- and international-level protocols for collecting and processing samples with the work coordinated by a research engineer:

  • How to choose subjects for samples? Which samples? With what minimum clinical data?
  • How should samples be taken? What should be the conditions for sending samples?
  • How should samples be processed to optimize their long-term conservation and use?

The last ten years work focused on the development of information systems (computer software) capable of optimizing the collection of biological and clinical data and of the interfaces required by those involved with the project including patients.
This required an initial study phase involving everyone working on the project (clinicians, engineers, IT specialists) on the construction of the modules of this database and of the biobank (from reception of samples to their preparation and conservation).
The development of computer tools paved the way for an increasingly ambitious and complete approach including:

  • a clinical database built to enable users to enter data ranging from very simple to much more complex elements like MRI data to construct real personal health records (PHR) with both write and read access for medical and paramedical professionals and patients alike
  • a biological database providing traceability, including for patients, of samples received, processed, stored and used along with results of any genetic tests run.

The study and implementation phases were both coordinated by a researcher in biology-epidemiology-biostatistics able to build bridges between the clinical, biological and computing fields.
An ethical study has also been run over 3 years at the European level as part of the European research project, Leukotreat.

How many patients are currently on the database? How many samples are stored in the biobank?

Currently there are over 2000 families of patients suffering from leukodystrophies registered on the database which makes up a total of over 7000 individuals (index cases and family members).
There are over 26,000 samples (blood, urine, plasma, serum, CSF, cell." >DNA, lymphoblast and fibroblast cell lines, muscles, nerves, cerebral tissues).

Could you remind us why such tools are useful for research into leukodystrophies?

There are many reasons why a database linked to a biobank is very useful:

  • Centralization of clinical and biological data to optimize monitoring of patients, their tests and samples and providing information on the natural history of illnesses for sufferers
  • Identification of the physiopathological mechanisms involved in the different forms of leukodystrophies thanks to analysis of stored biological samples. There is now a technique by which fibroblasts stored for 20 years can be transformed into central nervous system cells. This technique received this year’s Nobel prize for medicine.
  • Selection of homogenous patient populations to help optimize the identification of new genes which may play a role in illness or new markers for diagnosis and/or prognosis for each group of leukodystrophies
  • Selection of homogenous patient populations liable to benefit from innovative new therapies

Why is a clinical database necessary when digital patient health records are being developed in France? 

The aim of French digital patient health records (DMP or “Dossier Médical Personnel”) is to gather patients’ important health data for monitoring and treatment purposes but not to help optimize clinical, molecular or therapeutic research.
With rare diseases, the same data is required for patients’ daily treatment and for the development of innovative research. Data gathered therefore has to be as complete and as interfaced as possible to allow coordinated multi-disciplinary treatment and quality clinical research. An advantage of the information system which has been developed is that patients can learn about their own treatment and research into their illness by accessing vital information about diagnosis, monitoring and prognosis.

Could you give us examples of discoveries made possible thanks to the database and/or biobank?

Here are a few examples:

  • Identification of genes dating back 20 years which play a role in leukodystrophy development.
  • Research into correlations between genetic anomalies (genotype) and clinical characteristics (phenotype) for certain leukodystrophies: anomalies of the PLP gene and eIF2B genes.
  • Identification of markers for diagnosis and/or prognosis in pathologies linked to PLP and eIF2B mutations.
  • The natural history of patients suffering from PLP, eIF2B, GFAP and MLC1 mutations.

In 2014 the biobank and clinical database in Nancy will be inaugurated and their first stage will be to gather French data and samples. What impact will this have on research into leukodystrophies?

The biobank and the database will above all enable 20 years of work on behalf of patients and researchers to continue. Management by the ELA association will facilitate the constitution and optimisation of the collection of samples and data at European and international levels and enable as many researchers as possible to use that information. A more specific aim of this is to help speed up research in the therapeutic field for these rare diseases which is currently hindered by:

  • the lack of a natural history for the disease and markers for monitoring therapeutic effects
  • a continuing need for the most exhaustive listing possible of patients who may benefit from new therapeutic strategies.