A prime target for the development of anti-inflammatories

For the first time, scientists from the Institut Pasteur and Inserm have demonstrated the key role played by a particular molecule in intestinal infection. The study was published online in Immunity on December 12, 2013. The molecule, known as ATP, serves as a trigger signal for the inflammatory response targeting pathogenic agents. Using the Shigella flexneri model, the scientists have also shown how this bacterium is able to block the release of ATP in order to escape this defense reaction.

Discovery of this blocking mechanism could be a milestone in therapeutics: the development of new drugs that mimic this process could open up new possibilities for the treatment of chronic inflammatory diseases, such as Crohn’s disease.


© Inserm/Tran Van Nhieu, Guy

It has been known for some years that the extracellular presence of ATP – a molecule normally found inside cells – is able to alert the body to danger and trigger an inflammatory defense response. Such may be the case when tissue is damaged and cell contents are released. Yet, whether an infectious agent would be capable of triggering the same mechanism remained unclear.

The team led by Philippe Sansonetti, who heads the Molecular Microbial Pathogenesis Unit (Inserm U786 / Institut Pasteur), in association with scientists from the University of Toulouse and the Collège de France have recently shown in vitro and in vivo that infection with enteric pathogenic bacteria – in this study Shigella, Salmonella and enteropathogenic E. coli – induces the cell to actively release ATP into the extracellular environment: in the presence of the bacterium, intestinal epithelial cells open cell surface channels, allowing ATP molecules to escape. By binding to extracellular receptors, ATP triggers a chain of reactions that drive the inflammatory immune response designed to eliminate the threat of infection.

The scientists also proved that the Shigella flexneri bacterium is capable of blocking this release of ATP by injecting an enzyme directly into the infected cell. The enzyme acts by closing the channels. This is the first time a pathogen has been observed to have the ability to suppress this mechanism, thus allowing it to escape defenses put in place by the body. This discovery underlines the importance of ATP as a key regulator of intestinal inflammation.

Although inflammation is a natural defense mechanism that plays an essential role in tissue response to attack, it persists abnormally in some cases. It then becomes chronic, and can lead to inflammatory diseases. These diseases result in a malfunction of the immune system, which attacks the body’s normal components. By showing this potential to halt the inflammatory process, the study highlights this process as a new, prime therapeutic target for the development of anti-inflammatory drugs.

Currently, there are no anti-inflammatory drugs on the market that targets the release of ATP. However, this release mechanism could have an important, as yet undefined part to play in the future treatment not only of certain chronic inflammatory diseases of the intestine, such as Crohn’s disease, but also other pathologies such as cancer, obesity, type 2 diabetes or arteriosclerosis.

EUCelLEX Project: assessment of the social issues raised by the use of regenerative medicine in Europe

The European EUCelLEX Project (Cell-based regenerative medicine: new challenges for EU legislation and governance), coordinated by Inserm for a three-year period, funding to the tune of €500,000 from the European Union. The project consists in a full examination of the application of the European rules regarding cell banks together with current practices in respect of the therapeutic use of human cells in the different countries concerned. The purpose is to submit the data obtained to the European Commission for it to draw up legislative measures in line with medical advances in this field. On 4 December the nine research teams in Europe and Canada met at the Political Sciences Research Centre in Paris (CEVIPOF) for the launching of the project. 

Biobanks: the future of regenerative medicine

Today, human biological specimens are seen as resources essential to advances in the life sciences and medicine. The analytical data obtained enable a better understanding of the various diseases and also make it possible to propose the appropriate treatment, notably in the field of regenerative medicine[1]. Gathering, storing, processing and distributing them are all done by the biobanks – key players in the transfer of scientific knowledge to clinical practice. These biological databanks will enable researchers to identify new clinical biomarkers and develop new therapeutic approaches such as regenerative medicine. In this field, research into stem cells continues to be promising, stimulating as it does the body’s self-healing ability.

Need for a legal definition of the use of human biological specimens at European level

From 2004 to 2006, the European Union adopted three directives governing cells and human tissues in order to standardise their acquisition, their storage and their use for therapeutic purposes. These directives apply specifically to tissue and cell banks, including cord blood strains and cells used for regenerative medicine. However, they were used in very different ways from one country to another. “At present, the European legal texts concerning the use of stem cells for research by the players in the public and private sectors are not such as to enable the efficient sharing of these resources in Europe, which may impede advances in research,“ explains Emmanuelle Rial-Sebbag, coordinator of the EUCelLEX Project.

Furthermore, scientific developments in the use of human cells centre around new legal and institutional issues. More particularly, the development of research infrastructures at European level (BBMRI-ERIC, FCrin[2]) means re-examining the relevance of all this in the light of rapidly expanding clinical practice which also has to take public health issues into account. Thus today, the areas of examination can be seen to be expanding, and hence the inadequacy of European legislation regarding cell research. It should added that certain parts of the process of translating basic knowledge, up to and including the marketing of new products, are unequally regulated, either by the national laws of the member states or by Europe.

The EUCelLEX Project objectives

It is within this context that the EUCelLEX Project’s chief objective is to examine current legislation concerning the therapeutic use of somatic cells, in both the public and private sectors and in a number of European countries.

To this end, the project aims to assess the relevance of current European legislation in order to provide the data needed to establish a European framework for the use of stem cells of every type (embryo, adult and IPS cells from cord blood) in the light of recent scientific, legal and institutional developments in Europe. To obtain a complete picture of the European situation, the legal study will be complemented by an examination of current clinical practices together with the many ethical recommendations throughout Europe. Starting with the observation that the entire translational process, from research to the marketing of a product, is only partially covered by the EU rules, the teams will need to examine the heterogeneous nature of the legislation due to the freedom of action allowed to the member states.

Initially, each of the partners in the project will need to examine the legislation and the policies in their respective countries governing the use of stem cells at both national and European level.

They will then compare current legislation with the practices that are due to develop stem cells in the near future, more especially in the research infrastructures to highlight the deficiencies and propose sustainable solutions. Special interest will also be paid to emerging such as “cell tourism” or the use of unproved therapies. For example, in some European countries doctors propose to use regenerative medicine techniques which have yet to be scientifically validated and which do not meet the safety criteria imposed by both French and European legislation.

The ultimate objective is to make recommendations to the European Commission so as to facilitate the use of stem cells for clinical purposes in a stabilised legal context.

Thus the results of the project will enable innovation in research and help the European to implement specific legislation in this field.


The 4 phases of the EUCelLEX Project:

1. Information gathering on the legal implementation of the directive on tissues and cells, with the focus on current European legislation and the regulations set forth at national level.

2. Integration of this knowledge into a wider analytical context covering the entire field, focusing on stem cells and the cord blood banks.

3. Make an in-depth analysis of the legislation, the literature, case law and the gathering of opinions on the various ethical aspects.

4. Create tools for the participation of the professional people involved and he key players in the questions raised by the use of stem cells.

The research partners in the EUCelLEX consortium, based throughout Europe and in Canada, will use their scientific, legal and ethical skills to highlight the issues raised by the use of stem cells for the medicine of tomorrow.


EUCelLEX – Cell-based regenerative medicine: new challenges for EU legislation and governance

(Reference : 601806)

The EUCelLEX Project is to be launched on 4 December 2013 and will be aided by the European Union (FP7) for a period of three years. It is coordinated by Inserm and involves nine partners based in seven European countries and Canada:

Inserm (coordinator), France:
Leibniz University, Germany:
Central European University, Budapest, Hungary:
Legal Pathway, Netherlands
Oxford University, England:
Medical University of Graz, Austria:
National Political Sciences Foundation, France:
KU Leuven, Belgium:
McGill University, Canada:


[1] Regenerative medicine is a multidisciplinary field of research whose clinical applications are based on the repair, replacement or regeneration of cells, tissues or organs in order to restore an impaired function, irrespective of the cause, including congenital anomalies, diseases, traumas and ageing. It uses a combination of several technological approaches designed to replace traditional grafts.

[2] Biobanking and Biomolecular Resources Research Infrastructure – European Research Infrastructure Consortium, French Clinical Research Infrastructure Network

A new Associated International Laboratory on the trail of an ‘electronic nose’ to sniff out Pulmonary Hypertension

crédit : ©Fotolia

Professor André Syrota, Inserm Chief Executive, and Professor Peretz Lavie, President of Technion, will sign the agreement to create a new Associated International Laboratory (AIL) on 17 December 2013. This artificial ‘electronic nose’ project brings together Inserm Unit 999 ‘Pulmonary Hypertension’ and the Russell Berrie Nanotechnology Institute Chemical Engineering department, directed by Professor Hossam Haick. This device should be able to differentiate the specific olfactory signatures of certain diseases by analysing the breath. This Franco-Israeli collaboration will focus its research on patients presenting risks of developing Pulmonary Hypertension (PH).

This Associated International Laboratory is added to the current list of 17 AILs and so strengthens the position of Inserm on the international stage. These associations between laboratories enable a team of French researchers and team of foreign researchers to work together on the same project.

André Syrota is pleased with this new collaboration: “This new AIL is a great example of scientific cooperation based on excellence and the complementary nature of the two research teams”. Professor Peretz Lavie, President of Technion, is delighted by the establishment of this new laboratory, which lays a new brick in the collaboration between Technion and one of the most prestigious institutions in France.

By combining the skills of the French team specialised in pulmonary hypertension with those of the Israeli team in nanotechnology, the aim of the researchers is to finalise the artificial nose.

Pulmonary hypertension is defined by a significant increase in pulmonary blood pressure, developing towards heart failure. It affects 15 people per million inhabitants (1 out of 67,000 in Europe). Symptoms initially occur on exertion (breathlessness, chest plain, dizziness).

This ‘electronic nose’ (project named NA-NOSE for PH) will be able to tell the difference between a ill person and a healthy person by analysing their breath.

This new process will offer the possibility of developing a device that can be used in a clinical setting, capable of detecting markers of the disease in a sample of breath, particularly in asymptomatic patients with risks of developing PH.

“Using this new technology, we will save time compared to current screening techniques that occupy highly qualified staff for a long time, particularly to perform cardiac ultrasound examinations and strength tests”. Furthermore, nothing would be possible without the contribution of the Israeli team, which is one of the best in the world for the development of nano-materials, remarks Marc Humbert, director of the Inserm/ Paris-South University joint research unit 999 ‘Pulmonary Hypertension: physiopathology and Therapeutic Innovation’.

The results of treating patients will then be listed to reduce diagnosis times. The researchers are mobilised to allow doctors to act early and improve the efficacy of the care given.

The researchers hope to define new biomarkers and therapeutic targets in pulmonary hypertension through this Franco-Israeli Associated International Laboratory.

Find out more about the ‘NA-NOSE for PH’

This scientific project is focused on several research directions:

– Separate the volatile compounds present in the olfactory signature using the ‘electronic’ nose and qualify them based on their respective masses (use of gas chromatography coupled with mass spectrometry).

– Search for the presence of proteins needed for olfactory signalling among the components of the pulmonary vascular wall.

– Identify the volatile compounds involved in the PH and analyse their functional role in vascular cells.

– Produce transgenic mice with high expression of functional olfactory receptors on their vascular cells with the goal of analysing the effect of this overexpression on inducing disease