The Details of Project

Name of WP Partners involved WP leader
WP1
Design and characterization of nanosystems
month 1 to month 30
INSERM, APHP,MUG UKER, UT, MPG, CEA-LETI, CEA-DSV, NanoPET, BRACCO CEA-LETI
WP2
Preclinical validation of nanosystems
month 6 to month 42
INSERM, APHP, MUG SDU, UKER, UT, CEA-LETI, CEA-DSV, NanoPET, SU, BRACCO MUG
WP3
GMP production of injectable products
month 1 to month 60
INSERM, APHP, UT, CEA-LETI, BRACCO BRACCO
WP4
Toxicological data and Risk Assessment
month 1 to month 60
INSERM, CEA-LETI, WizSoft, NanoPET, SU, BRACCO SU
WP5
Diagnostic & therapeutic use of nanosystems in atherosclerotic patients
month 1 to month 60
INSERM, APHP, AMC, BRACCO APHP
WP6
Ethics and Regulatory files
month 1 to month 60
INSERM, APHP, IT, AMC, UT, NanoPET, BRACCO, Edinethics INSERM
WP7
Dissemination, training and exploitation
month 1 to month 60
INSERM, IT, CEA-LETI, CLINAM, WizSoft, NanoPET, BRACCO, Edinethics CLINAM
WP8
Management and coordination of the project
month 1 to month 60
INSERM, IT, NanoPET, BRACCO IT

Objectives of each WP:
WP1:
The objectives of this WP are:

  • The design at the lab scale and complete physicochemical characterization of nanosystems i) for molecular imaging and treatment of plaque atheroma and ii) therapy of stroke.
  • The selection of the three best nanosystems, one for targeted imaging by MRI or PET, one for stroke therapy with loaded tPA and one for plaque therapy with anti-inflammatory drugs. Nanosystems will be subsequently preclinically tested under WP2.

WP2:
The objective of WP2 is to achieve the pre-clinical validation of all systems created by NanoAthero.
The nanosystems will be evaluated for in vitro hemocompatibility and complement activation assays. Nanoparticles either eligible for passive targeting to plaques or linked with targeting ligands, and loaded with imaging compounds or active agents will be screened in vitro, ex vivo, and in vivo. Pharmacokinetic experiments will provide the information for the establishment of dosing schedules, duration of treatment and imaging results.

WP3:
The objective of WP3 is to support the preparation of the IMPD for the following systems:
• Nanosystem for imaging of thrombus
• Nanosystem for thrombolytic treatment of thrombus for stroke
• Nanosystem for plaque imaging, including a blood pool MRI agent
• Nanosystem for plaque therapy

WP4 :
WP4 objectives will be to proceed for regulatory toxicology evaluation of the systems:
• Toxicological data of selected nanosystem for imaging of thrombus
• Toxicological data of selected nanosystem for thrombolytic treatment of thrombus for stroke
• Toxicological data of selected nanosystem for plaque imaging
• Toxicological data of selected nanosystem for plaque therapy
Within WP4, we will also conduct a comprehensive hazard assessment of all the NanoAthero systems across the product life cycle from completing animal studies, through GMP manufacturing, toxicology and ethics, especially prior to entering clinical studies in humans. Introduction of means and tools for risk mitigation and control will provide risk control according to quality and safety principles of medical products and the EU guidelines.
We will assess the efficacy of the nanoparticles in diagnosis and treatment of atherosclerosis in the context and design of the specific project NanoAthero systems.

WP5:
To obtain clinical support for targeted-imaging and therapeutic nanosystems in atherothrombosis:

  • Evaluate local delivery of i.v. Nanocort in surgically-removed plaques (plaque phenotype, phenotype of inflammatory cells extracted from plaques, biomarkers);
  • Clinical proof of concept of in vivo P-selectin targeting with 99mTc-fucoidan by head-to-head comparison of molecular SPECT with ‘gold-standard’ histopathology of excised carotid plaques;
  • Randomized, clinical trial to test the efficacy of the most promising, preclinically (WP2)-validated, novel nanosystem using multi-modality imaging protocols in patients with atherosclerosis

WP6:
A broad range of advanced methods are needed in NanoAthero such as new medical procedures, patient consents, clinical trials, and animal experimentation in pre-clinical studies. Due to legal and ethical requirements of this study, involving nanoparticles, patient samples and animal models, the NanoAthero partners are especially committed to compliance with the legal regulations governing these areas of research (WHO, GHTF, etc.) and with a sound ethical approach. All EU regulations regarding animal experimentations, housing, professionals (86/609/CEE, 2003/65/CE), including the Treaty of Lisbon, will be rigorously followed.

WP6 will lead and supervise all aspects including study design, toxicology models, efficacy assessment, GCP conduct, GMP controlled manufacturing, risk assessment and management across the entire life cycle according to Standard ISO EN 14971:2007 and Standard EN 13641:2002.

WP7:
The objective of WP7 is to raise the international and local awareness of NanoAthero and to enable its findings to be applied. Activities in WP7 are:
• Dissemination of Results: Targets are policy makers, the medical and scientific community, industry, public interests groups, teachers, and the media, with their corresponding methods of outreach.
• Stakeholder and Public Engagement: Engagement with relevant stakeholders (e.g. patients’ groups), and the general public as the project’s work develops will aim to raise awareness, allay potential concerns, and also provide a means to listen to and take account of lay and user perspectives.
• Training: An integral part of the project is to train the next generation of researchers in the emerging fields of nano-enabled therapeutic and diagnostic systems, drawing on the multi-disciplinary expertise of the partners.
• IP management: To develop an IPR strategy for know-how, techniques and outcomes of the NanoAthero project.
• Exploitation: To monitor business developments and opportunities during the course of the project and develop exploitation plans to provide the mechanisms for their uptake in the relevant medical and industrial contexts.

WP8:
This WP is related to the administrative and legal management of the project, the scientific coordination being done at the WP level.