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Europe Attacks the Prion

Understanding Transmissible Spongiform Encephalopathies

Atomic structure of yeast prion. Amino acids forming a helix are figured in blue, those forming a sheet in red. The flexible region of the prion is shown in orange.

Ever since the first appearance of mad cow disease in 1996, prion research has been an increasingly important research theme in the EU. Active from the beginning, the CNRS plays a major role in this effort in France.

Mad cow disease, scrapie (in sheep), and new variant Creutzfeldt-Jakob disease are all transmissible spongiform encephalopathies (TSEs), a family of disease whose infectious agent is of a new type: an abnormal form of the prion protein (PrP). Naturally expressed in organisms, PrP becomes a carrier of disease when it takes on a different spatial configuration.

In vitro models
Sylvain Lehmann and his team at the Institute of Human Genetics (IGH, CNRS) have been studying TSEs, and in particular the role of abnormal prions in triggering these pathologies. "We are using biochemical and cellular approaches to understand normal function of the protein PrP, about which little has been known until now. Our research programmes are also exploring the factors and mechanisms that influence the generation of pathological PrP", Dr. Lehmann explains. Along these lines, Dr. Lehmann has already participated in several European research programmes and between 1998 and 2001 was coordinator of a project studying the prion's intracellular pathways, in collaboration with research groups from Italy, Ireland, and Britain.
These prior research efforts have resulted in the elaboration of in vitro models of TSEs that consist of cultured mouse nervous system cells expressing the different forms of prion. "The advantage is that we are now to some extent free of animal models. Prion disease is a major European concern", Lehmann emphasizes, "and these in vitro models are accelerating things for us as we venture into new areas of research." Evaluating new therapeutic molecules now takes only a few days  as opposed to several months with animal  testing. In vitro models also facilitate fundamental research into the transmission mechanisms of TSEs.

Fibres de prion

© CNRS Photothèque. Ronald Melki

Fibers formed by the prion when it becomes transmissible. This image was obtained using electron microscopy just after the prion acquired transmissibility in a test tube in the laboratory. These fibers are identical to those found in the brain of individuals afflicted with Creutzfeldt-Jakob disease.

Vital funding
For the last year Sylvain Lehmann has been coordinating a project on the "molecular foundations of neurodegenerative processes in TSE" which brings together CNRS research teams with groups from the Grenoble Faculty of Medicine, the National Agronomic Research Institute (INRA), the University of Leeds, the Mario-Negri Institute of Pharmacological Research (Italy) and the University of Hamburg. The goal of this research  initiative is to study how prions, the metabolism of metallic ions, and oxidative stress are linked, in order to development preventive and therapeutic strategies for use against TSEs.

With the momentum from this project, Dr. Lehmann initiated the first international seminar1 on anti-prion therapies, organised in 2002 by the CNRS and funded 50% by the European Union. "European funding is vital", explains Lehmann. "Without these funds I would never have been able to set up my laboratory when I came back from the US in 1997, nor to hire post-docs."

1/ "TSE : New perspectives for Prion Therapeutics." Paris, december 1st-3, 2002.
View web site congres.igh

In the EC framework program 6 (FP6) a Network of Excellence on prion called “NeuroPrion” has been founded with 52 different laboratories involved: View web site
Sylvain Lehmann is a member of the Executive Committee and the Coordinating group of the Network and his laboratory is the representative of the CNRS in the network.




Sylvain Lehmann
Institut de génétique humaine (IGH)
Biologie des encéphalopathies spongiformes transmissibles

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