RPIB - Recherches Partenariales et Innovation Biomédicale

Use of fucoidan as a diagnostic and therapeutic ligand of intravascular thrombi in cardiovascular pathology – FucoThrombo

Submission summary

Thrombotic events remain one of the main causes of mortality and morbidity in western countries, involving both the arterial and the venous part of the circulation: myocardial infarction, ischemic stroke, aneurysms, peripheral arterial disease, atrial thrombus and embolisms, phlebothrombosis and pulmonary embolisms. One main challenge is to develop new diagnostic and therapeutic tools able to detect and treat vulnerable thrombi before clinical expression. For these purpose we identified and patented low molecular weight fucoidan (LMWF) as a powerful ligand of intravascular thrombi in vivo. Fucoidan refers to a type of polysaccharide, which contains substantial percentages of L-fucose and sulphate ester groups, mainly extracted from brown seaweed and able to mimetic Sialyl Lewis X, the endogenous saccharidic motif recognized by platelet P-selectin abundantly expressed in all types of thrombi. The scientific objectives of FucoThrombo are to optimize production of LMWF at a medical grade and to develop further diagnostic in imaging and therapeutic applications for lyse of endovascular thrombi. FucoThrombo project will first enhance the purity of crude fucoidan batches currently produced by Algues & Mer company in an academic-enterprise partnership. For this purpose FucoThrombo will develop new chemical and physicochemical processes as well as analytical tools and quality controls..The new processes will be applied to purification of LMWF from fucoidan batches and to the subcontracted preparation of a GMP form. FucoThrombo will extent the use of LMWF as a vector by chemically adding some specific residues, for molecular imaging of thrombi in different modalities (PET, MRI), and for specifically targeting recombinant tissue Plasminogen Activator (rt-PA) to the thrombus. Therefore, the project will be covered by a transdisciplinary approach including 1) chemistry, 2) in vivo proof of concept in imaging technologies, and 3) preclinical therapeutic proof of concept that vectorization of rt-PA by modified LMWF significantly enhances its fibrinolytic capacity. Valorisation will be the production of medical grade LMWF by a company which would gain an international leadership in the field, and the development of new applications in collaboration with other companies specialized in nuclear imaging, magnetic resonnance imaging, and with pharmaceutical companies.

Project coordination

Jean-Baptiste Michel (Inserm 698 and ADR Paris 7 Cardiovascular Remodeling)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

A&M Algues et Mer
UNIVERSITE PARIS 13 Laboratoire de Bio-ingénierie de polymères cardiovasculaires
U698 Inserm Inserm 698 and ADR Paris 7 Cardiovascular Remodeling

Help of the ANR 679,278 euros
Beginning and duration of the scientific project: December 2013 - 42 Months

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