Page 390

AVAILABLE AND EMERGING DISEASE-MODIFYING THERAPIES a

GLOBAL IMMUNOSUPPRESSION

Medication Options

Status as of 1999

Putative Mechanisms Of Action

Cyclophosphamide

Off label use in the U.S. and Europe

Global reduction of T-cell population

Azathioprine

Off label use in the U.S. and Europe

As above

Glucocorticosteroids

Off label use in the U.S. and Europe

As above

Methotrexate

Off label use in the U.S. and Europe

As above

Total lymphoid irradiation

Off label use in the U.S. and Europe

As above

Paclitaxel

Phase II Clinical Trials

As above

2-Chlorodeoxyadenosine

Phase III Clinical Trials

As above

Mitoxantrone

Phase III Clinical Trials

As above

IMMUNOMODULATION

Therapeutic Strategy

Medication Options

Status as of 1999

Putative Mechanisms Of Action

1) Inhibit T-cell receptor/peptide/MHC-II interaction

Altered peptide ligands

Phase I/II

Block or compete with the binding of encephalitogenic peptides to the MHC-II molecule

Copolymer

Approved for relapsing forms of MS in the U.S. and Europe

Block or compete with the binding of encephalitogenic peptides to the MHC-II molecule

TCR vaccination and TCR peptide vaccination

Phase I

Generation of antibodies against peptides within the TCR

IL-10 , TGF b

Phase I/II

Immunomodulation; reduce MHC-II molecule expression

Interpheron Beta

Approved for relapsing forms of MS in the U.S. and Europe

Immunomodulation; reduce MHC-II molecule expression

2) Induction of T-cell anergy

Antibodies to B7 or molecules

Preclinical testing

T cells are anergised when TCR/peptide/ MHC-II interaction occurs in the absence of co-signalling

aAdapted from Waubant and Goodkin 1997.


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement