Treatment of Multiple Sclerosis with Azathioprine

Abstract

Azathioprine (AZA) has been the immunosuppressant drug most commonly used in multiple sclerosis (MS) and has even been adopted as a standard treatment in some centers, especially in France and Germany (Sabouraud et al. 1984; Lhermitte et al. 1987; Ventre et al. 1985; Kappos et al. 1988). Its use has been based on the hypothesis that MS is an autoimmune disease, a hypothesis which depends on its resemblance to experimental allergic encephalomyelitis (EAE) (see Chap. 8). This hypothesis has been strengthened by the development of chronic relapsing models of EAE in guinea-pigs, rats and mice whose course and clinical features bear a close resemblance to MS (Lassmann 1983). However, although antibodies and T cell responses against myelin antigens that induce EAE in animals have been demonstrated in patients with MS, these responses are also found in normal subjects and in patients with other neurological diseases (Leibowitz and Hughes 1983; Martin et al. 1990; Olsson 1990). Thus the autoimmune hypothesis, although arguably the most likely, has not been established beyond doubt. Consequently trials of immunosuppressive treatment in MS do not have a solid theoretical basis and must be regarded as partly empirical.