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Innovative therapeutics for the prototype autoimmune disease, myasthenia gravis

Objective

We will develop novel, specific, therapeutics to treat the model autoimmune disease, myasthenia gravis, which is caused by antibodies to the muscle acetylcholine receptor (Ache). The therapeutics (to be tested extensively in vitro and in vivo experiments) will target different aspects of the immune response and involve
(a) ex vivo immunoadsorption of the anti-Ache antibodies by immobilized polypeptide fragments of the Ache;
(b) protection of the Ache and reduction of B cell activation by modified non-pathogenic engineered monoclonal anti-Ache antibodies;
(c) selection of active subtractions of normal human lag for in vivo intravenous lag (Ivy) therapy; (d) induction of mussel tolerance by the use of recombinant Ache polypeptides;
(e) peptide vaccination against a dominant T cell receptor;
(f) peptide:MHC multimedia complexes to identify T cells ex vivo and tolerate them in vivo; (9) antilogous, Specific-specific, tolerogenic dendrite cells for in vivo use;
(h) combinations of selected therapies; (I) for the more efficient therapies, we will study gene expression levels by micro array technology in order to explore their mechanisms of action, and to identify potential new drug targets.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

HELLENIC PASTEUR INSTITUTE
Address
127,Vassilissis Sofias Av. 127
11521 Athens
Greece

Participants (7)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Avenue De La Resistance 133
92350 Le Plessis-robinson
DIAMED EUROGEN N.V.
Belgium
Address
Transportstraat 4
3980 Tessenderlo
KAROLINSKA INSTITUTE
Sweden
Address
Solnavagen 1
171 77 Stockholm
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
John Radcliffe Hospital, Headley Way
OX1 2JD Oxford
UNIVERSITE DE PARIS-SUD XI
France
Address
Avenue De La Resistance, 133 - Hopital Marie Lanne
92350 Le Plessis-robinson
UNIVERSITY OF MAASTRICHT
Netherlands
Address
Dr Tanslaan 10
6229 ET Maastricht
WEIZMANN INSTITUTE OF SCIENCE
Israel
Address
Herzel Street 2
76100 Rehovot