Gpi-ceruloplasmin, analogs thereof, and methods of use

Details Gpi-ceruloplasmin, analogs thereof, and methods of use Gpi-ceruloplasmin, analogs thereof, and methods of use

C - Chemistry, Metallurgy

12

N

C12N 15/53 (2006.01) A01K 67/027 (2006.01) A61K 35/12 (2006.01) A61K 38/44 (2006.01) A61K 48/00 (2006.01) C07H 21/00 (2006.01) C07K 16/40 (2006.01) C07K 16/46 (2006.01) C12N 5/12 (2006.01) C12N 9/02 (2006.01) C12N 15/85 (2006.01) C12Q 1/00 (2006.01) C12Q 1/26 (2006.01) C12Q 1/68 (2006.01) G01N 33/573 (2006.01)

Patent

CA 2218200

The present invention relates to ceruloplasmin having a unique glycosylphosphatidyl-inositol moiety (GPI-ceruloplasmin) and analogs thereof that anchors this form of ceruloplasmin to the cell surface of astrocytes in the mammalian central nervous system (CNS) and to leptomeningeal cells that cover the CNS. The invention also relates to cDNA sequences encoding said GPI-ceruloplasmin, and analogs thereof, and recombinant plasmids and host cells for expression. The invention also provides monoclonal antibodies to the protein, the nucleic acid sequences and their use in diagnosis, research and therapy. The invention further relates to use of said GPI-ceruloplasmin, and analogs thereof, to treat conditions where toxic levels of ferrous iron play a role, such as Parkinsons' disease, Alzheimers' disease, amyotrophic lateral sclerosis, aceruloplasminemia and Hallervorden-Spatz disease.

L'invention porte sur une céruloplasmine renfermant une fraction spécifique de glycosylphosphatidyl-inolsitol (GPI-céruloplasmine) et ses analogues, qui fixe cette forme de céruloplasmine à la surface cellulaire d'astrocytes dans le système nerveux central (SNC) des mammifères, ainsi qu'aux cellules leptoméningées qui couvrent le SNC. L'invention porte également sur des séquences d'ADNc codant la GPI-céruloplasmine et ses analogues, ainsi que sur des plasmides recombinants et des cellules hôtes pour leur expression. L'invention présente des anticorps monoclonaux pour la protéine, ainsi que sur des séquences d'acides nucléiques et leur emploi à des fins de diagnostic, de recherche et de thérapie. Enfin l'invention décrit l'utilisation de la GPI-céruloplasmine et de ses analogues pour traiter des affections où le niveau toxique du fer ferreux joue un rôle, comme dans la maladie de Parkinson, la maladie d'Alzheimer, la sclérose latérale amyotrophique, l'acéruloplasminémie et la maladie d'Hallervorden-Spatz.

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