Enhanced Suppression of Experimental Allergic Encephalomyelitis by Combination Chemotherapy with Duazomycin-A and 6-Mercaptopurine

Abstract

Experimental allergic encephalomyelitis (EAE) is a demyelinating disease that is widely held to be the result of a delayed hypersensitivity reaction of an "autoimmune" type. The discovery of effective therapy for this disease could have important clinical implications for human diseases of hypersensitivity as well as for the field or organ transplantation. Hoy et al.(1) were the first to use thiopurines in the treatment of EAE. Since that time several other antineoplastic drugs have proved effective in transiently suppressing clinical and histologic evidence of disease during the period of drug administration (2-5). With all these agents, however, it is usual for manifestations of EAE to develop after discontinuation of therapy .The use of combination chemotherapy of EAE in the present study was suggested in part by successes with drug combinations in the therapy of some neoplastic diseases (6) and by reports of the enhancement of theiopurine activity by glutamine antagonists in general (7, 8) and by Duazomycin-A ( Nacetyl-6-diazo-5-oxo-~-norleucine) (DZ'M) , in particular (9, 10).In the present study, attempts were made to suppress EAE by treating with 6-mercaptopurine (6-MP) and DZM alone and in combination. The data indicate that DZM enhances the effectiveness of 6-MP in EAE.

Prolonged azathioprine treatment of non-remitting multiple sclerosis

“…In the mid 1960s the exact nature of the immunological mechanisms of multiple sclerosis were unclear. However, it seemed reasonable to attempt chronic immunosuppressive therapy with agents more potent and reliable than corticosteroids and ACTH, analogous to the data from experimental allergic encephalomyelitis (Hoyer et al, 1962;Paterson and Drobish, 1969;Vogel and Calabresi, 1969). Therefore, patient selection criteria and a chronic treatment protocol using purine analogues were established in 1964 and continued to the present.…”