Promotion of central nervous system remyelination using monoclonal autoantibodies
AssigneeMayo Foundation for Medical Research
InventorsMoses Rodriguez, David Miller, Kunihiko Asakura
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Abstract
Monoclonal IgM antibodies which promote central nervous system remyelination when given to a mammal afflicted with a demyelinating disease are disclosed. These antibodies show multi-organ autoreactivity, and recognize both surface and cytoplasmic determinants on glial cells.
Claims19
A method of stimulating remyelination of central nervous system axons in a mammal in need of such therapy which comprises administer to said mammal an effective amount of a monoclonal autoantibody selected from the group consisting of mAb SCH 94.03, SCH 79.08, O1, O4, A2B5, HNK-1, active fragments thereof, and natural or synthetic autoantibodies having the characteristics thereof.
A method of stimulating the proliferation of glial cells in central nervous system axons in a mammal in need of such therapy which comprises administering to said mammal an effective amount of a monoclonal autoantibody selected from the group consisting of mAb SCH 94.03, SCH 79.08, O1, O4, A2B5, HNK-1, active fragments thereof, and natural or synthetic autoantibodies having the characteristics thereof.
A method of treating a demyelinating disease of the central nervous system in a mammal in need of such therapy which comprises administering to said mammal an effective amount of a monoclonal autoantibody selected from the group consisting of mAb SCH94.03, SCH79.08, O1, O4, A2B5 and HNK-1, active fragments thereof, and natural or synthetic autoantibodies having the characteristics thereof.
A in vitro method of stimulating the proliferation of glial cells from mixed cell culture comprising:
- a) culturing a mixed cell culture containing glial cells under condition sufficient for cell proliferation;
- b) introducing into the mixed culture an effective amount of a monoclonal autoantibody selected from the group consisting of mAb SCH94.03, SCH79.08, O1, O4, A2B5, HNK-1, active fragments thereof, and natural or synthetic autoantibodies having the characteristics thereof, thereby producing a monoclonal antibody-treated mixed culture;
- c) maintaining the culture of step b) under conditions sufficient for proliferation of monoclonal antibody-treated cells, thereby resulting in the proliferation of glial cells in the mixed culture;
- and
- d) harvesting the glial cells from the mixed culture.
The method of claim 18 wherein the mixed culture is obtained from rat optic nerve.
The method of claim 18 wherein the mixed culture is obtained from rat brain.
A method of stimulating remyelination of central nervous system axons in a mammal in need of such therapy comprising:
- a) culturing glial cells under conditions sufficient for cell proliferation thereby producing a glial cell culture;
- b) introducing into the glial cell culture an effective amount of a monoclonal autoantibody selected from the group consisting of mAb SCH94.03, SCH79.08, O1, O4, A2B5, HNK-1, active fragments thereof, and natural or synthetic autoantibodies having the characteristics thereof, thereby producing a monoclonal antibody-treated glial cell culture;
- c) maintaining the culture of step b) under conditions sufficient for proliferation of monoclonal antibody-treated cells;
- d) harvesting the monoclonal antibody-treated cells from the culture, thereby obtaining glial cells;
- and
- e) introducing the glial cells obtained in step d) into the central nervous system of the mammal, thereby stimulating remyelination of central nervous system axons.
A pharmaceutical composition comprising, as the active agent, an active fragment of a monoclonal autoantibody selected from the group consisting of mAb SCH94.03, SCH79.08, O1, O4, A2B5, HNK-1, and natural or synthetic autoantibodies having the characteristics of mAb SCH94.03, SCH79.08, O1, O4, A2B5 or HNK-1.
Dependencies are inferred from the claim text.