Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof
Patent
1996-03-13
1999-09-28
Scheiner, Toni R.
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Monoclonal antibody or fragment thereof
4241451, 4241561, 514 2, 530350, A61K 39395, A61K 3800
Patent
active
059584092
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system which usually presents in the form of recurrent attacks of focal or multifocal neurologic dysfunction. Attacks occur, remit, and recur, seemingly randomly over many years. Remission is often incomplete and as one attack follows another, a stepwise downward progression ensues with increasing permanent deficit.
Clinical disease is associated with blood-brain barrier dysfunction; infiltration of the central nervous system by mononuclear cells, mainly macrophages and T lymphocytes, and serum products; and demyelination (Harris J. O., et al., Ann. Neurol. 29:548 (1991); Kermonde A. G., et al., Brain 113:1477 (1990)).
Presently the nature of autoantigens responsible for multiple sclerosis is not known, nor is the action which triggers the autoimmune response. One popular theory involves the similarity of a viral protein to a self antigen, which results in autoreactive T cells or B cells recognizing a self antigen. Whereas B-lymphocytes produce antibodies, thymus-derived or "T-cells" are associated with cell-mediated immune functions. T-cells recognize antigens presented on the surface of cells and carry out their functions in association with "antigen-presenting" cells.
Currently no practical and efficacious treatments for multiple sclerosis exist. Thus, the development of a method for treating multiple sclerosis would be of immense benefit.
SUMMARY OF THE INVENTION
The present invention relates to a method of treating multiple sclerosis in a mammal. The invention is based on the discovery that tumour necrosis factor (TNF) has a role in the pathogenesis of multiple sclerosis and experimental allergic encephalomyelitis (EAE).
The method comprises administering to a mammal a therapeutically effective amount of an anti-tumour necrosis factor (anti-TNF) antibody which ameliorates the effects of multiple sclerosis. A therapeutically effective amount can be administered in the form of a single dose, or a series of doses separated by intervals of days, weeks or months.
Another method comprises administering to a mammal a therapeutically effective amount of a soluble TNF receptor which ameliorates the effects of multiple sclerosis. A therapeutically effective amount can be administered in the form of a single dose, or a series of doses separated by intervals of days, weeks or months.
Another method comprises administering to a mammal a therapeutically effective amount of a compound which is capable of blocking TNF production, its effects and/or tumour necrosis factor receptor signal transduction (anti-TNF compound).
The anti-TNF antibody, soluble TNF receptor or anti-TNF compound can be administered together with a pharmaceutically-acceptable vehicle. In a preferred embodiment administration of said antibody, soluble receptor or anti-TNF compound is by injection directly into the central nervous system of a human being. Injection directly into the central nervous system can be by injection directly into the lumbar cerebrospinal fluid (intrathecally). In another embodiment administration of said antibody, soluble receptor or anti-TNF compound is intravenously.
The present invention further relates to a pharmaceutical composition comprised of a pharmaceutically-acceptable carrier and a multiple sclerosis-therapeutically effective amount of anti-TNF antibody which ameliorates the effects of multiple sclerosis, soluble TNF receptor which ameliorates the effects of multiple sclerosis or anti-TNF compound.
The benefit of the method of therapy of the subject invention is that it provides an efficacious treatment for multiple sclerosis.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a histogram and a graph illustrating the kinetics of weight changes and clinical signs during acute phase chronic relapsing experimental allergic encephalomyelitis (CREAE) induced in Biozzi AB/H mice.
FIG. 2 is a histogram illustrating blood-brain barrier permeability to cells and protein during acute phase CREAE.
FIG. 3 is a graph illustrating
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Baker David
Feldmann Marc
Turk John Leslie
Johnson Nancy A.
Kennedy Institute of Rheumatology
Scheiner Toni R.
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