Fp7: Energy (Finland)

Funding Source/Programme

University of Rennes, Department of Biopharmaceutics, UPRES EA 3892 is seeking to join a research proposal in the course of elaboration as partner on the following themes:

- HEALTH-2007-2.2.1-5: from basic spinal mechanisms to spinal cord disease and trauma

- HEALTH-2007-2.4.1-6: understanding and fighting metastasis
- HEALTH-2007-2.4.1-7: improving targeted drug delivery to cancer cells for cancer therapeutics other than gene therapy

Description

Theme: Targeting metastasis at the cerebrospinal level using nanoparticulate carriers
Objective: We can have a significant role in projects aiming to set up new approaches to fight metastasis in the cerebrospinal fluid (neoplastic meningitis, NM). The use of nanoparticulate carriers for anticancer agents could allow the targeting of cancer cells and/or the control of the drug release.

Our competency: 1) The development of drug loaded-nanoparticles functionnalized with ligands to target specific cells and 2) the pre-clinical pharmacokinetic evaluation at the spinal level in animals (simultaneous microdialysis in the epidural space and in the cerebrospinal fluid – CSF -  for measuring in situ drug concentrations and study of the biodistribution of the nano particulate carrier).

Context: Metastasis in the cerebrospinal fluid (NM) remains a devastating complication of primary CNS or systemic tumors. The treatment options of NM are very limited and therapeutic outcomes are poor. The exact incidence of brain metastasis is unknown because of the lack of cancer registry document specific to that malignancy. In the Unites States, an estimation of 98 000 to 170 000 new cases diagnosed each year has been made.

Intrathecal chemotherapy remains a mainstay of treatment for NM and there are very few drugs used clinically (methotrexate, cytarabine, thiotepa and topotecan). Furthermore, the efficacy of these drugs is limited because of a short half-life within the CSF. Hence, the development of new strategies for intrathecal use of these drugs (or of other drugs) are of paramount interest if they can target the cancer cells within the CSF or if they can prolong the concentration drug profile within the CSF. The development of particulate drug delivery systems (e.g., nanoparticules, nanoemulsions) could avoid too high concentrations in CSF responsible for local toxicity, and could allow a prolonged release allowing less frequent intrathecal injections. Moreover, the development of functionalized nanocarriers (with covalent chemical grafting of cell-specific ligands on the particle surface) could target the cancer cells in CSF increasing the efficacy.

In a more prospective view, it could also be considered to develop multifunctional diagnostic and therapeutic (so called “smart”) nanoparticules. These nanoparticules may include the therapeutic molecule(s), a magnetic resonance imaging contrast agent to improve imaging diagnostic of residual disease, a cell specific targeting moiety, and a reporter.  Such “smart” nanostructures will eventually be able to detect residual malignant cells in vivo, to pinpoint their location in the CSF compartment, to kill the cells, and to report back that the loaded drug has reached the intracellular target. The principles driving this approach are modularity and multifunctionality, i.e., creating functional building blocks that can be snapped together and modified to meet the particular demands of a given clinical situation.

Contact

Pascal Le Corre, Professor of Biopharmaceutics at University of Rennes 1
Laboratoire de Pharmacie Galénique et Biopharmacie - UPRES EA 3892
Faculté des Sciences Pharmaceutiques et Biologiques
2 Avenue du Pr. Léon Bernard - 35043 Rennes Cedex - France
Tel. [phone]
Fax [phone]
[e-mail]
FP7: Health (France, 05.03.)

Funding Source/Programme

Health-2007-2.1.1-4: Characterisation and variability of the microbial communities in the Human Body

Description

Theme: Mechanisms of adaptation and biodiversity of microorganisms pathogenic for humans
Objective: We can have a significant role in projects of which the objectives are to understand the mechanisms of adaptation of pathogenic bacteria or to characterise the genome content of bacteria present in the human body and study their variability.

Key-words:  bacteria – human – infectious diseases

Our competency: Our academic team will strengthen its expertise in the use of genetic chips to study the simultaneous expression of several genes and the definition of regulatory schemas in target microorganisms. The team's expertise in transcriptome technology will be further advanced by creating different mutants (inactivated on chosen genes) or substituting a functional gene in naturally muted strains. Molecular biology techniques (chips, RT-PCR, sequencing) studied in fundamental research will be developed for diagnostic purposes. Changes in genetic expression of target pathogens will be analyzed, using a microcosm system or static or dynamic studies on defined surfaces or cell cultures. Actually, we are working on Staphylococcus aureus, Salmonella Typhimurium and Porphyromonas gingivalis. We have close links with the practitioners, so we have access to large collection of clinical strains.

Context: With the real support of the Microbiology Pole of the Rennes University Hospital, our team oriented its theme towards the "risk of infectious diseases" based on fundamental and applied studies in relation with clinical research. Our research activities have also evolved, with a strong focus on objectives of
clinical medicine:

- identification of genes implicated in the colonization of pathogenic microorganisms

- study of the mechanisms of colonization and expression of pathogenicity
- approach to the phenomenon of "re-emergence"
- link with different study projects with clinical applications (in terms of resistance to xenobiotics) and hospital epidemiology. The dynamics of spread of bacterial causing nosocomial and community-acquired infections in different populations will be studied via the conception of models. This work will call upon the use of tools for molecular identification and epidemiological analysis. This axis of research will be based on competencies in epidemiology of infectious diseases present in the team and upon experience acquired in characterization of genomic plasticity.